Cell Cycle 2 Flashcards
High levels of cyclin correspond to what?
high activity of cyclin, Cdk
What are the three Cdks we need to know? What are they involved in?
- Cdk1 (M, but also S for Cdk1/2-cycA)
- Cdk2 (G1/S transition, S, possibly M)
- Cdk4 (G1)
- involved in cell cycle
The active site of Cdks is blocked in the absence of what?
cyclin
*note, cyclin can also interact directly with Cdk substrates
Cyclins are classified into four different groups based on what?
when they function in the cell cycle and the timing of their expression
What are each of the cyclins corresponding to each phase and what Cdks do they bind to?
G1: cycD, binds to Cdk4
G1/S: cycE, binds Cdk2
S: cycA, binds Cdk2
M: cycB, binds Cdk1
cycB corresponds to what phase, binds what Cdk?
M phase, binds Cdk1
Cdk1-cycB
cycA corresponds to what phase, binds what Cdk?
S phase, binds Cdk2
Cdk2-cycA
Cdk1/2-cycA
cycE corresponds to what phase, binds what Cdk?
G1/S checkpoint, binds Cdk2
Cdk2-cycE
cycD corresponds to what phase, binds what Cdk?
G1 phase, binds Cdk4
Cdk4-cycD
Cyclins can interact directly with Cdk ______.
substrates
What is required for full Cdk activity?
phosphorylation by the Cdk-activating kinases (CAKs)
Cdk7, forms trimer with cyclin H and Mat1
**
Cdk binds cyclin, not going to get you full activity. What is needed for full activity?
phosphorylation by CAK
Cdk inhibitors (CKIs) help suppress Cdk activity. In what phase are these important for?
G1 phase
*know p27 (inhibits G1/S and S-Cdks, activates cyclin D-Cdk4)
What is the E2F network?
- they have DNA binding domains and drive expression of E2F network; and dimerization
**
What is the job of the retinoblastoma protein?
to regulate E2F
fix
What happens if pRB does not act?
- no control of E2F-dependent gene expression
* pRB keeps E2F form binding *** and DNA
Mitogen
growth factor
When cyc-Cdk acted on by mitogens, what happens?
fill in
as soon as pRB is phosphorylated
E2F is made
fill
What two responses occur secondary to double-strand break?
huge signal transduction
- rapid response
- delayed response
ATM (kinase), phosphorylates another kinase (Chk2) which phosphorylates Cdc25A, causing something to be broken down
Cdk2-cyclin is kept inactive (no start)
fix/fill
diagram
Immediate cell cycle arrest is caused by which response to a double-strand break?
rapid response
ATM has two roles, what are they?
- phosphorylate Chk2
- phosphorylate p53, making it stable and active
If DNA cannot be repaired, what does p53 do?
illicits programmed cell death
What is one of the most highly mutated?? thing in cancer?
p53
What is the evolution of a tumor?
- begins with mutations that provide a cell with competitive growth advantage
- over many years, descendants of that mutant cells acquire additional mutations to overcome a variety of regulatory barriers that block cell proliferation
- additional mutations promote genomic instability to enhance the rate of mutation
What is the advantage of tumor cells?
- no longer responds to growth factors, unregulated, can grow as much as it wants; gives it advantage over regular cells
- can’t undergo programmed cell death
- multiple mutations occur causing above changes and more
fill in
eventually, cell becomes malignant and invades other areas?
What are oncogenes?
- hyperactive cancer-promoting mutant gene
- tend to be genetically dominant
- normal gene version is called a proto-oncogene
90% of all human cancers are carcinomas - what is this?
a malignant tumor of epithelia
probably because epithelial tissues proliferate throughout life
know p16 NK4a?
old, aging cells express this
puts break on cell division
binds Cdk4 and inactivates that complex
it is a tumor suppressor gene
fix
Many human cancers are associated with mutations in one component of what?
the pRB module
** only one mutation in pRB module is necessary to drive cell cycle entry
