Articles Blocks 3-5 Flashcards
How does acetylation affect chromatin?
Open, active
How does methylation affect chromatin?
Depends on residue modified
What do movers do?
Remodel chromatin to move nucleosomes and allow transcription
What are the two categories of readers?
Chromodomain and bromodomain
What do writers do?
Add modifications
What do shapers do?
Mutation in histone protein itself alters function
Exosomes vs Microvesicles (ectosomes); subcategories of microvesicles
Exosomes- small, arise in the endosomal system, released upon fusion with plasma membrane
Microvesicles- larger, directly bud from the plasma membrane; apoptotic bodies, large oncosomes
What mediates clathrin-independent endocytosis?
Lipid rafts and caveolins
What Extracellular Vesicles promote sperm-egg fusion?
CD9 carrying EVs
Role of extracellular vesicles in retrovirus infection
Can carry viral proteins, receptors or RNA
What cells do tumor derived EVs alter to establish a tumor microenvironment?How can EVs affect fibroblasts?
Immune cells, endothelial cells, fibroblasts, mesenchymal stem cells; convert fibroblasts in Cancer-associated fibroblasts or myofibroblasts
What is an example of miRNA that induces cell proliferation?
miR-222 induces activation of PI3/AKT pathway
How does aberrant messenger RNA cause neurodegenerative disease?
Long term activation of integrated stress response- phosphorylation of alpha subunit of eukaryotic translation initiation factor 2 (eIF2), mediated by PERK, GCN2, PKR, and HRI (Sensor molecules)
What triggers sensor molecules?
ER stress, amino acid deprivation, viral infection, heme deprivation
What is the outcome of the integrated stress response?
Increased translation of specific mRNA, decreased global mRNA translation
Two pathways to activate NF-kappaB
Canonical or Alternative
What activates canonical pathway; what is this pathway critical for?
Diverse factors: TNF, IL-1, LPS; immunity, inflammation, apoptosis inhibition
What is NF-kappaB made up of in canonical pathway?
p50 and RelA subunits
What inhibits NF-kappaB in canonical pathway?
IkBa
What phosphorylates IkBa to allow NF-kappaB to enter cell nucleus and initiate transcription?
IKK (IkB kinase)
What activates the alternative pathway? What is this pathway important for?
CD40, RANK, BAFF; B cell maturation, formation of secondary lymphoid organs, production of high-affinity antibodies
What is NF-kappaB made up of in the alternative pathway?
p100 and RelB subunits
What inhibits NF-kappaB in the alternative pathway? What activates NF-kappaB? How?
Inhibited by p100; IKKa phosphorylates P100 to convert it to p52
What stimulates IKKa?
NFkB inducing kinase (NIK) phosphorylates IKKa
How does NF-kappaB promote neoplasia?
Evasion of apoptosis
Acquisition of limitless replicative potential
Induction of angiogenesis
Induction of invasion and metastasis
NF-kappaB’s role in apoptosis
Prosurvival and anti-apoptotic protein signaling
NF-kappaB’s role in limitless replicative potential
Transcription of cyclin D1
NK-kappaB’s role in angiogenesis
Transcription of IL-8 and VEGF (angiogenic)
What is self renewal of stem cells?
Can divide without differentiation
How is the PI3K-AKT-mTOR signaling pathway involved in cancer?
Constitutively activated, mediating proliferation, survival, nutrient uptake, metabolic activity, protein synthesis
PI3K-AKT-mTOR pathway
GF binds RTK, activates PI3K, phosphorylates PIP2 to PIP3, PIP3 activates AKT, which stimulates mTOR (HIF activation), NFkappaB, inhibits apoptosis
What inhibits PI3K?
PTEN
What is the role of Alpha1 antitrysin?
Protect lung from neutrophil elastase, also antiinflammatory; in transplant recipients, increase regulatory T cells
What secreted by adipocytes regulates energy balance?
Leptin
Effect of type II diabetes in adipocytes
Decreased GLUT4 expression
Increased RBP4, which causes increased inflammation through TLR 4 to activate inflammasome
Hepatitis virus B protein involved in carcinoma
HBx
What two factors give cryptococcus neurotropism?
Immune-shielding polysaccharide capsule
Cell-wall immunomodulatory laccase
Which TLRs recognize cryptococcus??
TLR2 and TLR9
What molecules are important in recruitment of M1 macrophages in cryptoccus infections?
IFN gamma, IL6, GM-CSF, S1P
What are two predisposing factors to cryptococcus?
HIV (low CD4+ T cells)
Autoantibodies to GM-CSF
Shape and structure of ebola virus (filovirus)
Filamentous, enveloped
What is Magnesium’s role in the cell?
Essential cofactor for ATP production, and many enzymatic reactions
Shiga toxin composition and end result
A and B toxin, inhibits protein synthesis
IBD is associated with what deficiency? why?
Vitamin D; Vit D acts as immunomodulator, antiinflammatory
What factors are associated with increased 1,25 alpha hydroxylase production in the kidney?
PTH, FGF23
What transmembrane receptor is critical for FGF23?
Klotho
What is Vitamin D’s role in the intestinal barrier integrity?
Maintains apical junctional complexes
