Week 6 Review - No Path Flashcards
Do activated cyclin-dependent kinases promote cell cycle progression, or do they stop the cell cycle?
They promote cell cycle progression
Name three ways the cell controls the activity of CDKs.
- Phosphorylation - ACTIVE when phosphorylated.
- Degradation via Ub-proteasome.
- Transcriptional changes.
What is a CKI?
CDK inhibiting protein
Describe the normal function of an activated (phosphorylated) CDK-cyclin.
CDK-cyclin-P phosphorylates (inactivates) Rb –> keeps Rb from holding onto E2F –> E2F goes to nucleus to upregulate DNA synthesis enzyme transcription
What is p53? How does the p53 protein work?
It is a tumor suppressor that can sense DNA damage in both G1 and G2 cell cycle stages. If DNA damage is present, p53 stops the cycle and upregulates p21 transcription. p21 is a cyclin-dependent kinase inhibitor (CKI) that helps stop the cell cycle to allow for DNA repair.
Name one disease that is characterized by inheritance of one defective p53 gene, predisposing patients to multiple cancers all over the body.
Li-Fraumeni syndrome
A 8-week old baby presents to your clinic with an absent red reflex in one eye. What do you suspect and what is the mechanism behind this?
Hereditary retinoblastoma - inheritance of one defective Rb gene. Rb protein is unable to sequester E2F –> constitutive transcription of DNA synthesis genes –> high susceptibility to developing eye tumors and other cancers.
Do receptor tyrosine kinase pathways promote growth, or apoptosis?
Growth
Which protein is ultimately phosphorylated in the PI3K receptor tyrosine kinase pathway that promotes cell survival?
RTK ligand binding –> bunch of steps –> activated PKB (aka Akt) dissociates from membrane to phosphorylate Bad –> inhibition of apoptosis
What is the function of the Ras protein in the Ras/MAPK RTK pathway?
It is activated by SOS guanine exchange factor (grab help, Ras!), Ras-GTP activates his brother Raf (a MAPKKK) –> –> MAPK –> promotion of cell growth and division
What would happen if the GAP (GTPase activating protein) on Ras became mutated? Is there an example of this that we learned?
Constitutive cell growth promotion by MAPK –> cancer
Yeah! Neurofibromatosis type 1 (NF1) is exactly this!
How many mutations of a proto-oncogene are required for loss of growth inhibition?
one
How many mutations of a tumor suppressor gene are required for loss of growth inhibition?
two
A defect in the ____________ pathway is thought to be the underlying mechanism for Lynch syndome-associated cancers. The molecular hallmark for this disease is _________ instability.
DNA mismatch repair and microsatellite instability
What is APC and what does it do? What cancer syndrome is it associated with?
APC is a tumor suppressor that binds beta-catenin, keeping beta-catenin from going to the nucleus to upregulate transcription of growth-promoting genes.
Hereditary APC mutation is associated with familial adenomatous polyposis syndrome (FAP)
What causes Fanconi Anemia? Name 4 clinical manifestations.
Mutation in FANC (DNA repair gene)
- Short stature
- Developmental delay
- Odd wrist curvature
- Missing or extra digits