Molecules to Disease Flashcards
Select the correct option regarding the IKK complex:
- The IKKꞵ subunit gets activated through the phosphorylation of the activation loop by the NEMO subunit.
- The IKK complex directly ubiquitinates the I𝛋B inhibitor and sends it to degradation.
- The IKKα subunit can be inactivated through autophosphorylation.
- The alternative NF-𝛋B pathway is activated through NIK and the IKKꞵ subunit.
- The canonical NF-𝛋B pathway activations mainly depends on the catalytic activity of the IKKꞵ subunit.
NFkB class
The canonical NF-𝛋B pathway activations mainly depends on the catalytic activity of the IKKꞵ subunit.
Select the incorrect option regarding NF-κB:
- It can’t be activated by receptors recognizing extracellular PAMPs.
- Promotes the expression of several antiapoptotic genes.
- NF-𝛋B autocrine loops can contribute to leukemia development.
- Promotes the expression of its own IκB inhibitor resulting in a negative feedback loop.
- NF-𝛋B can be activated intracellularly by DNA double strand breaks.
NFkB class
It can’t be activated by receptors recognizing extracellular PAMPs.
Select the correct option regarding the processing of p100 in the alternative NF-𝛋B pathway:
- The processing of p100 generates an active RelB subunit.
- The processing of p100 is dependent on the activation of the IKKα subunit.
- The processing of p100 mainly occurs in the canonical NF-𝛋B pathway.
- The alternative NF-𝛋B pathway depends on the direct degradation of p100 by caspases.
- The activation of NEMO is essential for the processing of p100.
NFkB class
The processing of p100 is dependent on the activation of the IKKα subunit.
Select the correct statement regarding the NF-𝛋B signaling pathways:
- RelA/p65 is a subunit that participates exclusively in the alternative NF-𝛋B pathway.
- NIK is a critical component of the canonical NF-𝛋B pathway.
- The IKK complex is solely responsible for the degradation of NF-𝛋B dimers.
- The NF-𝛋B pathway is activated by the interaction of TNF-α with its receptor.
- The alternative NF-𝛋B pathway can operate independently of p100 processing and still mediate immune responses.
NFkB class
The NF-𝛋B pathway is activated by the interaction of TNF-α with its receptor.
Select the correct statement regarding the regulation of NF-𝛋B activity?
- NF-𝛋B inactivation only occurs in the cytoplasm.
- IκB-α only binds to NF-𝛋B in the cytoplasm to inhibit its activity.
- NF-𝛋B can negatively regulate itself by promoting the expression of IκB-α and SOCS1.
- NF-𝛋B can be activated by sumoylation in the nucleus.
- A20 can activate NF-𝛋B activity by modulating TRAF6.
NFkB class
NF-𝛋B can negatively regulate itself by promoting the expression of IκB-α and SOCS1.
Which of the following statements correctly explains the link between inflammation and cancer through NF-𝛋B?
- NF-𝛋B activation is only associated with viral infections and has no connection to cancer.
- NF-𝛋B is activated by inflammatory stimuli, and its constitutive activation has been linked to cancer development.
- NF-𝛋B prevents cancer cell growth by inhibiting the G1 to S phase transition of the cell cycle.
- NF-𝛋B activation reduces the production of cytokines and growth factors, limiting cell proliferation.
- Constitutive NF-𝛋B activation induces apoptosis in cancer cells, preventing tumor growth.
NFkB class
NF-𝛋B is activated by inflammatory stimuli, and its constitutive activation has been linked to cancer development.
Select the INCORRECT option regarding the ICOS receptor:
- The ICOS intracellular tail has a motif that can recruit both p85 and p50α regulatory subunits of PI3K.
- ICOS signaling results in high levels of IL-4 production.
- The ICOS intracellular tail contains binding motifs for GRB2 and PI3K recruitment.
- ICOS participates in positive costimulatory loops by upregulating CD40L.
- ICOS can provide co-stimulatory signaling in absence of CD28 on some T cell secondary responses.
co-stimulatory
The ICOS intracellular tail contains binding motifs for GRB2 and PI3K recruitment.
Select the correct option regarding the Tumor Necrosis Factor Receptor (TNFR) superfamily:
- They activate the NFAT, MAPKs and NF-𝛋B, but not the PI3K/AKT signaling pathways.
- They are important for controlling the pool of effector and memory T cells.
- They are not expressed on naïve T cells.
- They recognize cysteine-rich domains on their ligands.
- They have intracellular binding motifs for TRAF and GRB2 adaptor proteins.
co-stimulatory
They are important for controlling the pool of effector and memory T cells.
Select the correct statement regarding effector T cell activation:
- T cell activation requires only the engagement of the T cell receptor (TCR) with peptide/MHC complexes.
- Co-stimulatory receptors on T cells enhance signals from the TCR and are essential for full activation.
- Naive T cells can be activated by recognizing self-peptides in the presence of CTLA-4 co-activatory receptors.
- CD28 acts as an inhibitory receptor during T cell activation.
- The immune synapse is formed solely by TCR signaling without involvement of co-stimulatory receptors.
co-stimulatory
Co-stimulatory receptors on T cells enhance signals from the TCR and are essential for full activation.
Which of the following statements best describes the function of CD28 during T cell activation?
- CD28 acts as a negative co-stimulatory receptor that suppresses T cell proliferation.
- CD28 does not influence cytokine production during T cell activation.
- CD28 is involved exclusively in the regulation of memory T cells, with no role in naive T cell activation.
- CD28 enhances T cell activation by binding to the B7-1 and B7-2 ligands expressed on antigen-presenting cells.
- CD28 inhibits T cell activation by increasing the activation threshold required for T cell responses.
co-stimulatory
CD28 enhances T cell activation by binding to the B7-1 and B7-2 ligands expressed on antigen-presenting cells.
Which of the following correctly describes a function of PI3K upon CD28 activation in T cells?
- PI3K is responsible for converting PIP3 into PIP2, which recruits enzymes like AKT/PKB.
- PI3K is activated exclusively through the binding of the proline-rich PYAP motif in CD28.
- PI3K activation is involved in the production of second messengers PIP2 and PIP3, which lead to the activation of downstream proteins like AKT, mTOR, and NF-𝛋B.
- PI3Ks have intrinsic kinase activity that phosphorylates the YMNM motif in CD28.
- PI3K is activated only by co-stimulatory receptors like CD28 during T cell activation.
co-stimulatory
PI3K activation is involved in the production of second messengers PIP2 and PIP3, which lead to the activation of downstream proteins like AKT, mTOR, and NF-𝛋B.
Which of the following statements best describes the role of the complex formed by SLP76, Vav, and LAT in T-cell co-activation by CD28?
- This complex hydrolyzes PIP3 into PIP2, which activates PKCθ and calcineurin through the release of calcium.
- The complex serves as a platform for PLCγ1 activation, which hydrolyzes PIP2 into DAG and IP3, leading to NF-κB and NFAT activation.
- SLP76, Vav, and LAT form a complex that directly activates the IL-2 gene promoter without the involvement of other transcription factors.
- The complex primarily activates the MEK–ERK pathway, which induces IL-2 production via NF-𝛋B alone.
- SLP76, Vav, and LAT are mainly responsible for the suppression of actin polymerization and cytoskeletal remodeling.
co-stimulatory
The complex serves as a platform for PLCγ1 activation, which hydrolyzes PIP2 into DAG and IP3, leading to NF-κB and NFAT activation.
Which of the statements is correct about the cellular responses to increases in intracellular concentrations of Ca2+?
1. Small intracellular increases in intracellular concentrations of Ca2+ are sufficient to activate NFAT and NFκB responses in T cells and neurons
2. The specificity of the response that a cell will give through Ca2+ signals depend only on its concentration
3. The specific cellular response to an increase in intracellular Ca2+ will depend on the magnitude, time and frequency of the signal
4. Under a small increase in intracellular Ca2+ concentration, the first pathway that to be activated in time is the NFκB-mediated
5. The specificity of the response that a cell will give through Ca2+ signals depend only on the magnitude of the stimulus
Calcineurin-NFAT
The specific cellular response to an increase in intracellular Ca2+ will depend on the magnitude, time and frequency of the signal
About the inhibitors of Calcineurin, CsA and FK506, choose the correct answer:
1. Both of them are selective NFAT inhibitors
2. CsA acts by forming a complex with cyclophilins (Cyp) which binds directly to Calcineurin, impairing its phosphatase activity
3. FK506 can bind directly to FKBPs and Calcineurin, impairing their activity
4. Answers a- and c- are correct
5. None is correct
Calcineurin-NFAT
CsA acts by forming a complex with cyclophilins (Cyp) which binds directly to Calcineurin, impairing its phosphatase activity
Which of the following is correct regarding calcineurin:
1. Calcineurin is a calmodulin-dependent serine-threonine kinase
2. One of the functions of calcineurin is to dephosphorylate NFAT
3. Calmodulin will bind Calcineurin if calcium levels are low in the cell
4. Autoinhibitory domain (AID) is the catalytic domain of the calcineurin complex
5. Cyclosporin A is an enhancer of Calcineurin’s phosphatase activity.
Calcineurin-NFAT
One of the functions of calcineurin is to dephosphorylate NFAT
About NFAT activation of T cells …
1. The lack of CD28 co-activation of T cells will leave the NFAT activation insufficient and drive cells into an anergy state.
2. The lack of CD28 co-activation of T cells will have no effect, as the NFAT activation is sufficient to drive cells into an active state.
3. The NFAT:FOXP3 complex is solely required for the activation of effector T cells.
4. The NFAT:AP-7 complex induces an immune response
5. Both FOXP3 and AP-1 binding NFAT differenciate T cells into the Th17 lineage.
Calcineurin-NFAT
The lack of CD28 co-activation of T cells will leave the NFAT activation insufficient and drive cells into an anergy state.
What is the function of STIM1 in calcium mobilization in T cells?
1. It activates calcium entry through CRAC channels and regulates Cav1.2 in the plasma membrane.
2. It inhibits calcium entry by blocking CRAC channels.
3. It decreases intracellular calcium concentration by binding to Orai1.
4. It increases intracellular calcium concentration by activating calcium pumps in the endoplasmic reticulum.
5. It directly activates calcineurin
Calcineurin-NFAT
It activates calcium entry through CRAC channels and regulates Cav1.2 in the plasma membrane.
What distinguishes oscillatory calcium activation from constant activation in the regulation of transcription factors (TFs)?
1. Oscillatory activation amplifies weak signals and confers selectivity in NFAT activation.
2. Constant activation increases specificity in NFAT activation.
3. Oscillatory activation activates TFs like NF-kB and reduces the need for calcium.
4. Constant activation prevents NFAT translocation to the nucleus.
5. Both types of activation generate the same effects on TFs.
Calcineurin-NFAT
Oscillatory activation amplifies weak signals and confers selectivity in NFAT activation.
About the Major Histocompatibility Complexes, choose the correct answer:
1. For both classes of MHCs, all their subunits are encoded by the HLA genes, located in the same chromosome of the genome
2. MHCs have a huge variety for Antigen-binding specificity, which is generated by rearrangement mechanisms of the mRNA
3. Interactions of the T-cell receptor complex with MHC I will determine T cell differentiation into a CD4-positive cell
4. The specificity of a given MHC to its antigen peptides is determined only by interactions with certain amino acid residues of the peptide
5. The interaction of the extracellular domain of a TRC with its corresponding MHC-antigen is sufficient to trigger the proper T cell response
TCR
The specificity of a given MHC to its antigen peptides is determined only by interactions with certain amino acid residues of the peptide
Regarding positive and negative selection mechanisms that operate in the development of mature T cells, choose the correct answer:
1. Only around 2% of the double positive (CD4+CD8+) cells are discarded after selection.
2. Only high affinity TcRs will survive after negative selection.
3. After the positive selection differentiation into CD4+ or CD8+ T cells, the development process is concluded and these cells are exported to periphery.
4. Defects in the negative selection process of immature T cells can give rise to autoimmunity or immunodeficiency.
5. TcRs in the thymus undergo selection by interacting with foreign peptides presented.
TCR
Defects in the negative selection process of immature T cells can give rise to autoimmunity or immunodeficiency.
What role do RAG-1 and RAG-2 play in TCR variability?
1. They introduce mutations in the CDR1 and CDR2 regions of TCRs.
2. They add nucleotides to TCR variable regions using TdT.
3. They recognize recombination signal sequences (RSS) and initiate somatic recombination in TCR genes.
4. They promote the rearrangement of CD3ζ chains.
5. They are involved in the post-translational modification of TCRs.
TCR
They recognize recombination signal sequences (RSS) and initiate somatic recombination in TCR genes.
Which of the following is the correct order of events in TCR activation?
1. MHC-peptide interaction, LCK activation, ITAM phosphorylation in the CD3𝞯 chain, ZAP70 recruitment, calcium influx.
2. ITAM phosphorylation, ZAP70 recruitment, MHC-peptide interaction, LCK activation, calcium influx.
3. MHC-peptide interaction, ITAM phosphorylation, LCK activation, ZAP70 recruitment, calcium influx.
4. MHC-peptide interaction, ITAM phosphorylation, ZAP70 recruitment, LCK activation, calcium influx.
5. LCK activation, MHC-peptide interaction, ZAP70 recruitment, ITAM phosphorylation, calcium influx.
TCR
MHC-peptide interaction, LCK activation, ITAM phosphorylation in the CD3𝞯 chain, ZAP70 recruitment, calcium influx.
Regarding the immune synapse…
1. TcRs and other key molecules in the T cell are arranged based on importance.
2. Despite T cells having only 1 synapse with an APC, this synapse will contain more than one TcR molecule with its corresponding co-activators.
3. The initial apex (cSMAC) of the synapse is formed by the adhesion molecules and their receptors, which recognised and attached to the APC.
4. After the initial contact, the synapse gets rearranged and the TcR is at the center (cSMAC), with co-activators (i.e. CD4) surrounding it close by (pSMAC).
5. All of them are correct
TCR
All of them are correct
Upon TcR activation …
1. The T cell will immediately liberate preformed cytokines to the extracellular space.
2. Molecules such as PLCγ, p38, VAV and LCK will bind adaptor proteins like SLP76.
3. Calcium released from the endoplasmic reticulum by IP3 will directly activate JUN and FOS transcriptional activity.
4. Actin polymerization is one of the earliest responses to TcR activation.
5. CD4+ cells will trigger an NFAT mediated response while CD8+ will trigger a NF-κB one.
TCR
Molecules such as PLCγ, p38, VAV and LCK will bind adaptor proteins like SLP76.
Mammalian cells can respond to the pathogen trough TLRs:
1. binding undirectly pathogen’s molecules after the action of one protease
2. all TLRs directly bind to the pathogen
3. TLRs can only respond to bacterial and viruses pathogens
4. TLRs can recognise their ligands in both cytoplasmic membrane and endosomal surface
5. TLRs can recognize their ligands in the cytosol
PRR
TLRs can recognise their ligands in both cytoplasmic membrane and endosomal surface
NOD-like Receptors (NLR):
1. they are the only ones that recognise host molecules
2. their ligands are only from bacteria
3. their main outcome is activating inflammatory caspases such as Caspase 1
4. their activation don’t need oligomerization
5. they have no relation in their downstream pathways with TLRs
PRR
their main outcome is activating inflammatory caspases such as Caspase 1
All the following molecules are TIR domain containing adaptors. Which one is a negative adaptor?
1. TRAM
2. SARM
3. MyD88
4. TRAF
5. MAL
PRR
SARM
What is the function of A20 in TLR signalling?
1. It is an adaptor that helps TRAF6 to bind TRIF
2. Ubiquitylate TRAF6 activing NF-KB signalling
3. De-ubiquitylate TRAF6 activing NF-KB signalling
4. Ubiquitylate TRAF6 repressing NF-KB signalling
5. De-ubiquitylate TRAF6 repressing NF-KB signalling
PRR
De-ubiquitylate TRAF6 repressing NF-KB signalling
In the regulation of Toll-like receptor signaling, which of the following mechanisms are not related to TRIF?
1. SARM inhibits TRIF
2. TRIF activates NF-κB
3. TRIF uses TRAM for interacting with TLR4
4. MyD88s activates IRAK4 recruitment
5. SARM binds to TRIF
PRR
MyD88s activates IRAK4 recruitment
SARM inhibits Toll-like receptor signaling through which of the following mechanisms?
1. Promotes TRIF degradation
2. Binds to TRIF to prevent the recruitment of effector proteins
3. Inactivates IRAK4
4. Blocks the recruitment of MyD88
5. Deubiquitinates TRAF6
PRR
Binds to TRIF to prevent the recruitment of effector proteins
Which is the only TLR that recognises DNA?
1. TLR1
2. TLR2
3. TLR4
4. TLR6
5. TLR9
PRR
TLR9
The following TLR assembles as a homodimer, select the incorrect one:
1. TLR1
2. TLR2
3. TLR4
4. TLR6
5. TLR9
PRR
TLR2
Select the right TLR3 ligand:
1. dsRNA
2. ssRNA
3. dsDNA
4. ssDNA
5. None is correct
PRR
dsRNA
What is the CORRECT role of MAVS (Mitochondrial Antiviral-Signaling Protein) during viral infection?
1. MAVS only activates immune responses from the mitochondrial membrane.
2. MAVS translocates to peroxisomes to produce delayed antiviral effects.
3. MAVS stays on the mitochondria and activates both mitochondrial and peroxisomal pathways.
4. MAVS on peroxisomes triggers antiviral effects that are independent of IFN.
5. MAVS is quickly degraded after viral detection, halting immune signaling.
PRR
MAVS on peroxisomes triggers antiviral effects that are independent of IFN.
Which of the following statements about STING (Stimulator of Interferon Genes) is INCORRECT?
1. STING is localized in the endoplasmic reticulum and translocates to the Golgi upon activation.
2. STING is activated by cyclic dinucleotides such as cGAMP, produced in response to cytosolic DNA sensing.
3. Upon activation, STING triggers the production of type I interferons and other pro-inflammatory cytokines.
4. STING can be directly activated by double-stranded DNA (dsDNA) in the cytosol.
5. STING plays a critical role in the innate immune response to microbial and damaged self-DNA.
PRR
STING can be directly activated by double-stranded DNA (dsDNA) in the cytosol.
Which of these statements is true about cytokines-JAK-STAT pathway:
1. Upon binding their specific receptors, cytokines share the activation of a common JAK kinase which is the same for all of them.
2. The CD4 T-cells can have different functional outcome, depending on the STAT activated they can differentiate to Th1 or Th2
3. JAK-STAT signaling pathway is isolated from the rest of the cell’s signaling process; they can’t activate MAPK cascade or mTOR.
4. STAT protein family doesn’t suffer any post-translational modification, as it impairs their capacity to transport to the nucleus.
5. STAT proteins lack DNA binding domains, so it is necessary for them to be paired with a second protein who has.
JAK-STAT
The CD4 T-cells can have different functional outcome, depending on the STAT activated they can differentiate to Th1 or Th2
Following the JAK-STAT signaling module, knowing it starts with these steps:
a. Receptor subunits dimerization induced by a cytokines
b. Reciprocal tyrosine phosphorylation of the JAK kinase
c. Receptor’s tyrosine residues get phosphorylated by JAK activity.
Choose the correct immediate following step in this pathway:
1. The receptor is internalized and interact with STAT
2. STAT’s residues get phosphorylated by JAK activity
3. Receptor’s phosphorylated residues act as a docking site for STAT proteins
4. Receptor’s phosphorylated residues block the binding of STAT
5. The phosphorylated receptor can dimerize and migrate to the nucleus
JAK-STAT
Receptor’s phosphorylated residues act as a docking site for STAT proteins
How does the K48 ubiquitin bind to substrates utilizing E3 ligase
1. Ubiquitin creates a covalent conjunction with lysine residue sites on substrates
2. The utilization of three different enzymes: an attachment enzyme, a conjugating enzyme and a ligase
3. The irreversible bind to lysine residues leading to suppression of cytokine signalling
4. It will require the 26S proteasome
5. Ubiquitin utilizes E2 Ligase in the binding process
JAK-STAT
Ubiquitin creates a covalent conjunction with lysine residue sites on substrates
Which of the following statements is FALSE about IL-12
1. Can be activated by macrophages and dendritic cells
2. Causes the activated of the cascade in STAT4 to promote TH2 cells
3. Activates proinflammatory functions in immune cells
4. Development of T H1 cells create a positive feedback loop
5. IFN-γ targets immune cells leading to increased antimicrobial activity and increased MHC expression
JAK-STAT
Causes the activated of the cascade in STAT4 to promote TH2 cells
Which of the following statements correctly distinguishes between sumoylation and polyubiquitination?
- Both sumoylation and polyubiquitination involve the formation of polyprotein chains on target proteins that mark them for degradation by the proteasome.
- Sumoylation modifies target proteins to alter their localization or activity, while polyubiquitination typically marks proteins for degradation.
- Sumoylation uses the same E2 conjugating enzyme as polyubiquitination to transfer SUMO to the target protein.
- Polyubiquitination involves the attachment of a SUMO protein to the target, while sumoylation involves the attachment of multiple ubiquitin molecules.
- Polyubiquitination is ATP-dependent while sumoylation is not.
JAK-STAT
Sumoylation modifies target proteins to alter their localization or activity, while polyubiquitination typically marks proteins for degradation.
Which of the following is NOT a proposed mechanism by which PIAS proteins repress transcription?
- PIAS proteins block the DNA-binding activity of a transcription factor.
- PIAS proteins recruit histone deacetylase (HDAC) to inhibit transcription.
- PIAS proteins promote sumoylation of the transcription factor to inhibit its transcriptional activity.
- PIAS proteins sequester transcription factors in subnuclear structures to inhibit transcription.
- PIAS proteins recruit co-activators like p300 or CBP to enhance transcription.
JAK-STAT
PIAS proteins recruit co-activators like p300 or CBP to enhance transcription.
According to the study, what is the role of OxPAPC in the development of acute lung injury (ALI)?
1. It inhibits the production of reactive oxygen species (ROS).
2. It reduces TLR4 expression in macrophages.
3. It triggers cytokine production and influences the severity of ALI.
4. It prevents the formation of oxidized phospholipids (OxPLs).
5. It is not a common lipid in lung tissues.
Acute lung injury article
It triggers cytokine production and influences the severity of ALI.
According to the study, what was the effect of the defect in ROS production (NCF1 mutants) in response to the H5N1 virus challenge?
1. It caused increased lung injury.
2. It resulted in reduced lung injury and no formation of OxPLs.
3. It led to increased TLR4 expression in macrophages.
4. It had no effect on lung injury.
5. It triggered higher cytokine production.
Acute lung injury article
It resulted in reduced lung injury and no formation of OxPLs.
What are the changes in NF-kB activity after acid induction in mice with different mutations compared to wild-type mice?
1. NF-kB activity of TLR4-deficient mice is significantly enhanced.
2. NF-kB activity of MyD88-deficient mice is similar to wild-type mice.
3. NF-kB activity of TRIF-deficient mice is higher.
4. NF-kB activity of TRAF6-deficient mice is significantly enhanced.
5. No change in NF-kB activity of all mice.
Acute lung injury article
NF-kB activity of MyD88-deficient mice is similar to wild-type mice.
What is the main function of TRAF6 in the TLR4 signaling pathway?
1. Inhibit TLR4 signaling.
2. Mediate ROS generation.
3. Activate NF-kB as a key signaling molecule.
4. Regulate the production of anti-inflammatory cytokines.
5. Promote MyD88 signaling.
Acute lung injury article
Activate NF-kB as a key signaling molecule.
Choose the INCORRECT option about H5N1 infection in vivo:
1. Elastance and wet to dry ratios are lower compared to a less pathogenic virus.
2. can trigger OxPLs and rapid onset ALI in vivo.
3. can induce ROS formation on primary human monocytes.
4. WT mice respond more severely than mice deficient in TLR4 and TRIF.
5. can induce TLR4 surface expression on primary human monocytes.
Acute lung injury article
Elastance and wet to dry ratios are lower compared to a less pathogenic virus.
Select the true statement about dual specificity kinases:
1. They can phosphorylate both tyrosines and threonines of the MAPKKs.
2. Dual specificity phosphatases act as “counter” enzymes by removing the phosphate group from MAPKs.
3. ERK1/2 and ERK5 are examples of dual specificity kinases.
4. Even though the dual specificity kinases phosphorylate two different sites, the phosphorylated kinases only need one phosphorylation in order to be activated.
5. Each dual specificity kinase acts on a specific MAPK in order to activate it.
MAPKs
Dual specificity phosphatases act as “counter” enzymes by removing the phosphate group from MAPKs.
Select the true statement about MAPKinases:
1. The activation of a MAPK leads to the dephosphorylation of the upstream MAP2K.
2. MAPKinases are found in humans, but not in plants nor yeast.
3. Scaffolds are essential to confer efficiency and specificity to signaling MAPKinases
4. The ERK MAPK signaling pathway is mainly activated in stress responses.
5. The kinetics of a MAPK do not have an important role in the biological outcome of the signaling pathway.
MAPKs
Scaffolds are essential to confer efficiency and specificity to signaling MAPKinases
There is more than one way to generate specificity in MAPK signaling pathways. Select the incorrect statement:
- Scaffold proteins help organize components into complexes, ensuring that specific MAPK pathways are activated.
- Spatial encoding increases the specificity of signaling because of subcellular compartmentation.
- Cross-pathway inhibition ensures that the right pathway is activated, increasing the specificity.
- By controlling the duration and timing of MAPK activation specificity is ensured and will lead to precise biological responses.
- Dual specificity allows for specificity in the MAPK pathway by two receptors being activated at once.
MAPKs
Dual specificity allows for specificity in the MAPK pathway by two receptors being activated at once.
Select the true statement about MAPKinases:
1. The main outcome of the JNK pathway is to regulate protein synthesis in the ribosome.
2. ERK is primarily involved in growth factor signaling and regulates cell proliferation and differentiation.
3. Scaffolds prevent signaling cascades from occurring in the cytosol, but enhance them in the endosome.
4. MAPK stands for Meiotic-Activated Protein Kinase and is exclusively involved in regulating meiosis in cells.
5. AMP hydrolysis is fundamental for the phosphorylation of each kinase
MAPKs
ERK is primarily involved in growth factor signaling and regulates cell proliferation and differentiation.
In order to activate the NF-kB pathway in response to DSB DNA damage:
1. Different DNA damage kinases can activate this pathway.
2. The signal has to be amplified by ELKS activation in the nucleus.
3. No matter the pathway, NF-kB activation is exclusively dependent on NEMO activation.
4. NF-kB is naturally found in the nucleus and upon ATM nuclear exit it will be activated to activate pro-survival gene expression.
5. NF-kB is activated upon IkB inhibitor degradation by the proteasome by a previous acetylation provided by the NEMO complex that leads to its ubiquitination.
NFkB article
No matter the pathway, NF-kB activation is exclusively dependent on NEMO activation.
What causes NEMO to exit the nucleus upon DNA damage:
1. Upon ubiquitination in the nucleus by ATM.
2. Upon phosphorylation in the nucleus by ATM.
3. Upon phosphorylation in the nucleus by the IKK complex.
4. Upon acetylation in the nucleus by ATM.
5. NEMO remains in the nucleus due to ATM phosphorylation which leads to IkB.
NFkB article
Upon phosphorylation in the nucleus by ATM.
The loss of phosphorylation of the NEMO substrate serine 85 upon DNA damage can be compensated by:
1. Ubiquitination
2. Methylation
3. Sumoylation
4. Ionizing radiation
5. Phosphorylation
NFkB article
Ubiquitination
How can new cancer therapies possibly be improved to avoid cancer cell survival:
1. By phosphorylation of serine 85
2. By enhancing NEMO phosphorylation
3. By introducing doxorubicin
4. By enhancing ubiquitination
5. By directly inhibiting the ATM-NEMO-NF-kB pathway
NFkB article
By directly inhibiting the ATM-NEMO-NF-kB pathway
What is the main role of the IKK complex in the NF-κB pathway after DNA damage:
1. The IKK complex phosphorylates the ATM in order to inhibit the NF-kB pathway.
2. The IKK complex can directly phosphorylate NF-kB, causing its nuclear translocation.
3. The IKK complex phosphorylates IκB, leading to its degradation and the release of NF-κB.
4. The IKK complex can be located in the nucleus upon DNA damage.
5. The IKK complex facilitates NEMO ubiquitination.
NFkB article
The IKK complex phosphorylates IκB, leading to its degradation and the release of NF-κB.
Select the true statement about the NF-kB pathway:
1. ATM phosphorylates IκB, leading to its degradation and NF-κB activation.
2. ATM directly binds to NF-κB and activates it by phosphorylation.
3. NEMO directly phosphorylates ATM, which will trigger NF-kB activation.
4. When the ATM is exported to the cytoplasm, it inactivates the IKK complex.
5. ATM directly phosphorylates NEMO at residue Serine 85.
NFkB article
ATM directly phosphorylates NEMO at residue Serine 85.
What is the primary function of the cGAS-STING pathway in the immune response?
1. To degrade foreign DNA/RNA molecules
2. To enhance phagocytosis of pathogens
3. To sense cytosolic DNA and initiate an antiviral response
4. Primary effect is the production of IFN
5. To trigger apoptosis or cell death in infected cells
cGAMP article
To sense cytosolic DNA and initiate an antiviral response
Why was HEK Cells (Human Embryonic Kidney Cells) were used to study cGAS-STING pathway?
- Because HEK cells overexpress cGAS
- Because HEK cells do not express cGAS
- Because HEK cells express STING but not cGAS
- Because HEK cell do not express STING but express cGAS
- Because HEK cell are easy to maintain
cGAMP article
Because HEK cells do not express cGAS
Which of the following best describes the role of STING in the cGAS-STING pathway?
1. STING directly binds cytosolic DNA to initiate an immune response.
2. Activated STING translocates to the perinuclear area, where it recruits TBK1 to activate downstream signaling.
3. STING acts as a transcription factor for the expression of interferon genes.
4. STING functions exclusively in the adaptive immune response by activating T-cells and B-cells.
5. STING, when activated, promotes autophagy.
cGAMP article
Activated STING translocates to the perinuclear area, where it recruits TBK1 to activate downstream signaling.
Why do we need to add dsDNA to HEK cGASlow to activate HEK STING bystander cells?
1. We don’t need it, HEK cGASlow doesn’t recognise it
2. dsDNA will stimulate HEK STING directly, needed to produce INF-β
3. HEK cGASlow needs a jump start of dsDNA to activate HEK STING
4. dsDNA is needed for all cGAS, also cGAS*, to activate HEK STING
5. HEK cGASlow does not need dsDNA but dsRNA
cGAMP article
HEK cGASlow needs a jump start of dsDNA to activate HEK STING
What is pIFN-β-Gluc used for?
1. It is used to measure directly the amount of cGAS enzymatic activation
2. It attaches to connexins, allowing the existence of gap junctions
3. It is a transcription factor that produces luciferase to see the cells
4. It will produce luciferase when cGAS-STING pathway is activated
5. As a plasmid used as a transporter
cGAMP article
It will produce luciferase when cGAS-STING pathway is activated
If we make a knock out blocking the formation of the MEF cell line’s gap junctions and co-culture them with a HEK STING cell line with their wild-type connexins, it will be expected that:
1. The cGAS catalytic activity in the MEF cells will be stopped
2. cGAMP will be produced and transferred to the nearby co-cultured HEK cells
3. We will observe strong STING clustering in the nearby co-cultured HEK cells
4. If we added CBX (inhibitor of gap junction assembly) to the culture, we wouldn’t see any effect in the fluorescence microscopy image obtained
5. The CMA will stop promoting the STING clustering in the MEF cells
cGAMP article
If we added CBX (inhibitor of gap junction assembly) to the culture, we wouldn’t see any effect in the fluorescence microscopy image obtained
After the infection of a certain cell line with a dsDNA virus that can’t replicate and kill the cell, but that has introduced the dsDNA to the cell’s cytosol, it is true that:
1. The cGAS-STING pathway won’t be activated, as it requires that the virus is actively replicating
2. Unless the viral infection produces effective viral particles, the nearby cells won’t be able to activate the STING clustering
3. The cGAS-STING pathway will be active and will produce cGAMP, and this can warn the nearby cells of the viral infection
4. The cGAMP produced in the infected cells will be liberated to the medium by exocytosis, to warn the bystander cells
5. The gap junctions are needed to pass the cGAS enzyme to bystander cells
cGAMP article
The cGAS-STING pathway will be active and will produce cGAMP, and this can warn the nearby cells of the viral infection
The CTLA-4 (Cytotoxic T Lymphocyte Antigen 4) level of expression in the membrane of T CD4+ and T CD8+ is regulated mainly by:
1. TRIM which is responsible for activating trafficking to the lysosomes in order to degrade CTLA-4.
2. T-Cell activating signal intensity.
3. It is constitutively expressed and is normally shown in the membrane.
4. The AP-1 and AP-2 clathrin proteins, which are responsible for trafficking CTLA-4 to the membrane.
5. All answers are correct.
co-inhibitory receptors
T-Cell activating signal intensity.
TIM-3 receptor is (select the correct answers):
1. More expressed in exhausted T-lymphocytes which have been exposed to chronic infections or cancer.
2. More expressed in tumoral infiltrated T-Lymphocytes with high interferon-gamma production.
3. Capable of promoting different cell responses depending on the coligand to which it joins.
4. a, b and c are correct.
5. a and c are correct.
co-inhibitory receptors
a and c are correct.
Which is the gold standard immunotherapy approved by the FDA (Food and Drug Association) in 2022 for the treatment of metastatic melanoma?
1. ADAM10/17 blockade.
2. Monotherapy with Nivolumab (mAb anti-PD1).
3. Monotherapy with Relatimab (mAb anti-LAG3).
4. Combined immunotherapy with Tremelimumab (mAb anti-CTLA4) and Pembrolizumab (mAb anti-PD1)
5. Combined immunotherapy with Nivolumab (mAb anti-PD1) and Relatimab (mAb anti-LAG3).
co-inhibitory receptors
Combined immunotherapy with Nivolumab (mAb anti-PD1) and Relatimab (mAb anti-LAG3).
Which domain in the cytoplasmic tail of PD1(Programmed Death Protein 1) is essential for the inhibition effect?
1. IgV domain
2. ITIM (Immunoreceptor Tyrosine-based Inhibitor Motif)
3. Transmembrane region
4. IgC domain
5. ITSM (Immunoreceptor Tyrosine-based Switch Motif)
co-inhibitory receptors
ITSM (Immunoreceptor Tyrosine-based Switch Motif)
Which of the following sentences about Herpesvirus Entry Mediator (HVEM) co-ligand is FALSE:
1. LIGHT and Lymphotoxin-α (LTα) can bind to HVEM.
2. The co-inhibitory receptor CD160 competes with the co-receptor BTLA for binding the same region of HVEM.
3. HVEM can also bind to glycoprotein D from Herpes Simplex Virus (HSV).
4. CD160 binding HVEM acts as a positive modulator of the immune response.
5. HVEM belongs to the tumor necrosis factor receptor (TNFR) superfamily.
co-inhibitory receptors
CD160 binding HVEM acts as a positive modulator of the immune response.
Which step of the BTLA (B and T Lymphocyte Attenuator) signaling pathway is FALSE:
1. The HVEM ligand binds with BTLA.
2. BTLA can interact with HVEM in cis or trans manners.
3. The phosphorylation of both ITIM and ITSM motifs is necessary for the recruitment of tyrosine phosphatases SHP-1 and SHP-2.
4. The recruitment of SHP-1 and SHP-2 leads to downstream signaling resulting in the activation of T-cell proliferation.
5. The phosphorylation of the Grb-2 motif leads to activation of the PI3K/Akt signaling pathway.
co-inhibitory receptors
The recruitment of SHP-1 and SHP-2 leads to downstream signaling resulting in the activation of T-cell proliferation.
Regarding the interaction and competition of caspase-8 and cFLIP, what sentence is true:
1. The heterodimer of caspase-8 and cFLIP L (long), don’t limit caspase-8 activity.
2. The heterodimer caspase-8 and cFLIP S (short) lead to the inhibition of caspase-8 activation.
3. cFLIP L can dimerize with caspase-8, which is still capable of performing both auto-proteolytic and trans-proteolytic cleavage.
4. The cut form of cFLIP L heterodimer with caspase-8, cannot promote the activation of nuclear factor-kB (NF-kB).
5. cFLIP is a dimer that cannot dimerize with caspase-8.
TNFRs
The heterodimer caspase-8 and cFLIP S (short) lead to the inhibition of caspase-8 activation.
The apoptosis signaling by CD95:
1. Requires an adapter protein called FADD with a CARD domain.
2. Does not need an adapter protein; it binds directly to caspase via its DD domain.
3. Requires an adapter protein called FADD with a DED domain.
4. CD95 uses both TRAF and FADD adaptors
5. Does not need an adapter protein; it binds directly to caspase via its DED domain.
TNFRs
Requires an adapter protein called FADD with a DED domain.
What processing needs a caspase to go through in order to be activated?
1. Proteolytic processing, afterwards, the effector caspase will commit the cell to apoptosis
2. Proteolytic processing, afterwards, the initiator caspase will commit the cell to necrosis
3. Proteolytic processing, afterwards, the zymogen caspase will commit the cell to apoptosis
4. Activation through a cleavage done by FADD, afterwards, the caspase will commit the cell to necrosis
5. Activation through a cleavage done by FADD, afterwards, the caspase will oligomerize and commit the cell to apoptosis
TNFRs
Proteolytic processing, afterwards, the effector caspase will commit the cell to apoptosis
Select the incorrect sentence about the TNFR signaling:
1. Mutations in CD95 or CD95L can lead to accumulation of peripheral lymphoid cells and to a fatal autoimmune syndrome.
2. The caspase 3 is an initiator caspase and the caspase 8 is an effector caspase.
3. The extracellular ligand-binding regions of the receptors are characterized by a variable number of cysteine-rich repeats.
4. NF-KB can induce multiple anti-apoptotic genes in order to prevent TNF alpha-induced apoptosis
5. Apoptosis signaling downstream TNFR is mediated by death by design.
TNFRs
The caspase 3 is an initiator caspase and the caspase 8 is an effector caspase.
The central role of AKT/PKB in apoptosis is:
1. To activate apoptosis through phosphorylation of different substrates
2. To limit apoptosis promoting phosphorylation in pro and antiapoptotic substrates.
3. It has no role in apoptosis regulation.
4. To activate apoptosis through dephosphorylation of substrates.
5. To limit apoptosis with only activatory phosphorylation in substrates.
TNFRs
To limit apoptosis promoting phosphorylation in pro and antiapoptotic substrates.
Regulation of TNFR1 responses, select the correct sentence:
1. Its pro-apoptotic branch is promoted by c-Flip activity
2. Its pro-suvival branch is promoted by the activity of the ubiquitin ligase Itch
3. Its pro-survival branch is promoted by JNK activation
4. Its pro-survival banch is dependent on de novo transcrition and translation
5. The pro-survival branch requires the activation of the adaptors TRADD and FADD
TNFRs
Its pro-survival banch is dependent on de novo transcrition and translation
