L5: Regulation of Cell Cycle & Apoptosis Flashcards
What regulates the cell cycle?Specify which one is direct and which one is indirect.
Regulated by 2 tumour suppressors:
- DIRECTLY by Rb (Retinoblastoma) protein
- INDIRECTLY by p53 tumour suppressor
If a cells doesn’t enter into an active cell cycle what does it do?
enters G0 - quiescent state
what would prevent a cell from entering the mitosis phase of the cell cycle?
if DNA replication is not completed in G2
what would prevent a cell from entering the anaphase stage of mitosis?
blocked if chromatids are not properly assembled on the mitotic spindle
where is the DNA damage check point? what happens if genome damage is detected?
R point in G1
if genome damage is detected entrance into S phase is blocked
in the S phase of the cell cycle, what happens if the genome is damaged
DNA replication is halted
Which are the cell cycle proteins?
cyclins, CDKS and CKI
What are cyclins?
proteins that are expressed in a specific manner during the cell cycle. They form a complex with cyclin dependent kinases, CDKs, and ACTIVATE them.
What are CDK?
Cyclin Dependent Kinases, that phosphorylate specific substrates at serine/threonine residues.
Which Cyclin Dependent Kinase Inhibitors are involved in the cell cycle
p21, p27 & p57 proteins
which point in the cell cycle is usually deregulated cancer cells?
R/Restriction point
After cells go through R point, what happens with the activated kinases?
After cells go through R-point
each activated kinase sequentially activates the next kinase and inhibits the previous kinase for the cell cycle to proceed smoothly without further regulation
Name the different kinases active during each phase of the cell cycle and the cyclins that activyate them.
1. Mitosis: CDK: CDC2 Cylin B 2. G1: CDK: CDK4/6 Cyclin D 3.G1 After R point: CDK: CDK2 Cylcin E 4 S: CDK: CDK2 Cyclin A S phase to G2 phase CDK: CDC2 aka CDK1 Cyclin A
During cell cycle progression the cyclin D-CDK4/6 complex becomes an active kinase that phosphorylates what?
Retinoblastoma (Rb) protein.
During cell cycle progression hyper-phosphorylation of Rb protein is dependent on what?
cyclin E-CDK2
During cell cycle progression hyper-phosphorylation of Rb protein allows what?
Hyper-phosphorylated Rb releases the E2F transcription factors to allow cells to go into S phase.
what does p53 function as?
as a DNA-damage inducible, DNA sequence specific transcription factor.
p53 co-ordinates what?
p53 co-ordinates the cellular response to genotoxic stress and has been called the ‘Guardian of the Genome’.
what is the most commonly mutated tumour suppressor?
p53
how does mutant p53 behave?
behaves as a dominant oncogene, which frequently spans the benign to malignanttransition step.
which CKIs inhibits
D-CDK4/6
p16 INK4A
p15 INK4B
p18 INK4C
p19 INK4D
which CKIs inhibit E-CDK2, A-CDK2, A-CDC2 and B-CDC2.
p57 Kip2
p27 Kip1
p21 Cip 1
