Lifengs Content Flashcards
What is the role of G1-CdK in the cell cycle?
Phosphorylates Rb, activating E2F which starts the cell cycle
What does E2F activation lead to?
Transcription of genes needed in S-phase.
What is the role of G1/S-CdK in the cell cycle?
Phosphorylates the inhibitory p27 and promotes S-Cyclin expression.
What is the commitment step in the cell cycle?
The transition to S phase from G1 via G1/S-CdK activity is the commitment step. The cell is committing to DNA replication.
What is the role of S-CdK in the cell cycle?
Initiates DNA replication, produces DNA polymerase.
What is the role of M-CdK in the cell cycle?
Promotes events in mitosis like DNA condensation.
How does p53 regulate CdKs in response to DNA damage?
Turns on p21, inhibiting G1/S and S CdKs.
How does Myc regulate CdKs in response to mitogen activity?
Increases D cyclin expression, activating G1-CdK.
What happens when Myc is overexpressed?
Leads to uncontrolled cell growth, tumorigenesis.
What is the role of Nim1 in response to nutritional status?
Inhibits Wee1, promoting cell cycle progression.
What is Wee1?
Wee1 is a kinase that phosphorylates CdKs, inactivating them.
What role does CdK1 play in the nucleus?
Protects nucleus from fragmentation.
What is inhibited during nutritional starvation?
Nim1 inhibits Wee-1 in response to nutritional starvation, this promotes the cell cycle.
What inhibits Wee1 in a positive feedback loop?
Active M-CdK complexes.
What is the function of Cdc25?
Removes phosphorylation on CdKs.
What activates Cdc25 in a positive feedback loop?
Phosphorylation of M-CdKs.
What is PP2A-BB5?
A phosphatase that regulates CdKs.
What is the most important subunit in the PP2A-BB5 protein?
The B subunits, this subunit effects selectivity, localization, and enzyme regulation.
When is subunit B55 activity highest?
During G1/G2 phase.
What happens to subunit B55 during early M phase?
Its activity is Inhibited when M-CdK concentration rises
When is subunit B55 re-activated?
After cyclin degraded in anaphase.
What are CKIs?
CdK inhibitory proteins.
What phase do CKIs predominantly regulate?
G1/S passage.
What does P27 inhibit?
G1/S Cdks and SCdks.
What increases P21 expression?
DNA damage and subsequently p53
What controls P21 expression?
p53.
What is Ink4 and what does it do?
its a CKI that inhibits C1CdKs and acts as a tumor suppressor
What is APC/C?
A ubiquitin ligase that adds ubiquitin to M-cyclins and securin during anaphase and ensures that all centromeres are attached before mitosis begins.
What activates APC/C?
Binding of Cdc20, stimulated by MCdks activity, activates APC/C.
What role does APC/C play in anaphase?
Degrades M-cyclin, promotes anaphase, and ensures centromere attachment
What is the role of APC/C in anaphase?
What is the role of APC/C in anaphase?
How is Cdc20 production stimulated?
By MCdks activity.
How does the Cdc20-APC/C complex work?
Recruits E1, E2, and ubiquitin to form a polyubiquitin chain, this is then used on the m cyclins.
What is the function of SCF in the cell cycle?
Ubiquitinates proteins, controlling G1/S cyclins.
What regulates Rb activity in normal cells?
Phosphorylation level of G1 cyclins.
How does Myc influence cell cycle progression?
Activates G1 cyclins, cdc25, and SCF subunits.
What is the role of p53 in the cell cycle?
p53 arrests cell cycle for DNA repair
What activates excessive proliferation signals like Myc?
mitogens binding to myc and actviating cascades
How is p53 activated by DNA damage?
ATM and ATR activate Chk1/Chk2, phosphorylating p53.
What role does Mdm2 play in p53 regulation?
Mdm2 decreases p53’s transcriptional activity
How does p53 prevent cells from leaving G1?
Activates TFs like p21, arresting the cell cycle.
ATM is activated by ____ DNA breaks
Double Stranded
ATR is activated by _ DNA Breaks
Single Strand
What proteins do Chk1/Chk2 phosphorylate?
Mdm2 and subsequently p53
What prevents MCdk activation after nuclear export?
14-3-3 protein holds it, arresting cell cycle.
What does SCF ubiquitin ligase degrade?
It activates FBox proteins, ubiquitinates G1/S cyclins
What are the structural features of initiator caspases?
Inactive monomers with prodomain, large and small subunits.
What activates executioner caspases?
Active initiator caspases cleave them.
What do active executioner caspases cleave?
Nuclear lamin and cytosolic proteins.
What initiates intrinsic apoptosis?
DNA damage leading to cytochrome c release.
What forms the apoptosome?
7 Apaf1 molecules and cytochrome c.
What is the role of cytochrome c in apoptosis?
it acts as an eat me signal and also binds to the card region of Apaf1
What is the structure of active executioner caspases?
Heterotetramers with two large and small subunits.
Heterotetramers with two large and small subunits. GARBAGE
Anti-apoptotic, bind to bak.
What is the function of the apoptosome’s center?
CARD recruits and binds procaspase 9.
What happens to cells not exposed to growth factors?
Enter quiescence (G0) via inhabition by p21
What is the effect of Myc activation on the cell cycle?
Enhances expression of cyclin D, Cdc25, E2F
How does mitogen/GF affect CdK regulation?
Increases D cyclin, G1-Cdk complexes expression
What role does p53 play in apoptosis?
It localizes to the mitochondrial membrane, binds Bcl2, leading to Bax MOMP formation.
What is the effect of Myc on apoptosis?
Myc activates p53 and Bim in response to excess growth factors, leading to apoptosis.
How do extrinsic and intrinsic pathways crosstalk in apoptosis?
Bid initates crosstalk. Bid is activated into tBid, linking pathways and promoting cytochrome c release.
What role do IAPs and anti-IAPs play in apoptosis regulation?
IAPs inhibit caspases; anti-IAPs bind IAPs, ensuring caspase functionality for apoptosis.
How do growth factors influence apoptosis?
Growth factors inhibit apoptosis by activating PI3K-Akt pathway, phosphorylating/inactivating Bad.
What triggers the intrinsic pathway of apoptosis?
DNA damage, leading to cytochrome c release via Bax and Bak proteins.
How do Bcl2 proteins regulate apoptosis?
Bcl2 proteins inhibit Bax, preventing MOMP, thereby regulating apoptosis.
What role do perforin and granzyme play in apoptosis?
Perforin creates channels; granzyme activates procaspases, leading to apoptosis.
What triggers the intrinsic pathway of apoptosis
DNA damage leading to the activation of initiator caspase 9 via the apoptosome.
How do initiator caspases lead to apoptosis in the intrinsic pathway
They cleave and activate executioner caspases
How does Myc influence apoptosis when there is excessive growth stimulus?
Myc activates p53 and Bim, leading to apoptosis through various pathways including Mdm2 inhibiti
How does p53 regulate apoptosis after DNA damage
It activates transcription factors for pro-apoptotic proteins like Bcl-2, Bax, and Apaf1, leading to mitochondrial membrane changes.
How do growth factors regulate apoptosis
They stimulate cell proliferation, suppress apoptosis, and promote protein synthesis that inhibits apoptotic pathways.
What are survival factors?
Factors required for cell survival that suppress apoptosis when bound to cell-surface receptors.
What is the function of IAPs (Inhibitor of Apoptosis Proteins)?
They inactivate caspases through their BIR domains and serve as inhibitors against death-inducing stimuli.
What initiates death ligand/death receptor mediated apoptosis?
The binding of death ligands (e.g., FasL) on cytotoxic T cells to death receptors (e.g., Fas/CD95) on target cells.
How can apoptosis be inhibited in the death ligand/receptor pathways?
By decoy CD95 receptors and the protein FLIP, which blocks caspase 8 and 10 activation.
How does Bad influence apoptosis in the absence of growth factors?
Unphosphorylated Bad complexes with Bcl-2, preventing it from inhibiting Bax, leading to MOMP.
