Cell Cycle Flashcards
(25 cards)
Which CDK-Cyclin complexes control passage through the restriction point?
Cdk4-Cyclin D and CDK6-Cyclin D
Which CDC cyclin complex controls entry into s phase
Cdk2-cyclin e
Which CDK cyclin complex controls passage through a phase?
Cdk2 cyclin a
Which cdk cyclin complexes control entry into mitosis?
Cdk1 cyclin a
Cdk1 cyclin B
Give some. DK inhibitor proteins
P16
P21
P27
How do growth factors affect cycling and CKIs?
Inhibit production of CKIs (cdk inhibitor proteins)
Promote production of cyclin d
How can cancer cells avoid apoptosis?
Upregulate anti apoptotic pathways
Downregulate apoptotic pathways
Give examples of down regulation of apoptotic pathways exploited by cancers
Loss of LKB1 pro apoptotic signal
Checkpoint defect CHK2
Mutations of DNA damage sensing system (eg p53)
Give examples of upregulation of anti apoptotic pathways exploited in cancer
Pro-survival signals eg BCL-2
Loss of sensitivity to apoptotic signalling eg decoy receptors
Oncogene activation eg ras
Give an example of a decoy receptor
Proteins which mimic TRAIL1 or 2 but lack functional activity
What does LKB1 do?
Signals low O2 or glucose
Inhibits mTOR
Prevents mTOR mediated cell growth/proliferation, angiogenesis, cell survival
Which cancer syndrome is as a result of mTOR overactivation?
Peutz-Jeghers syndrome
Many polyps in the GIT
Benign polyps but can become cancerous
What is MDM2?
P53 inhibitor
How are mdm2 and p53 regulated?
Inhibit each other
Mdm2 activates p53 export from nucleus
Mdm2 ubiquinates p53
How is mdm2 regulated
Arf aka p14 inhibits mdm2
Give examples of p53 actions
Activates death receptors; DR5 aka TRAIL2; Fas
Activates; Apaf-1; PUMA; NOXA; Bax
Inhibits Bcl-2
How do tumour cells avoid p53?
Mutations in initial signalling kinases eg ATM, ATR, CHK1, CHK2
Mutations of p53
Mdm2 over expression
Arf mutations
What is c-flip?
Caspase-like protein.
Shares same DED1 DED2 (death effector domains)
Lacks a cysteine residue at its binding site
So can bind death receptors but can’t continue the signal
Example of decoy receptor
How do cancers resist TRAIL? Via decoys?
Expression of TRAIL receptors 3, 4 and 5 which lack the death domain
Aka (DcR1, DcR2 and osteoprotegerin respectively)
Compete with genuine TRAIL receptors 1 and 2 to antagonise apoptotic signalling
List the methods of TRAIL signal evasion in cancer
Epigenetic silencing
Receptor gene mutation
Upregulation of decoy receptors (needs more evidence)
Increased c-flip activation
What does ras do?
Activates raf
Activated by a GEF
Activates the MAPK pathway
How is ras mutated in cancer?
Mutated to become constituently active
Codon twelve glycine for valine
Affects ability to hydrolyse GTP to GDP
What key pathways does ras activate?
MEKK
raf
PI3K
What does BAD do?
When unphosphorylated, is pro-apoptotic When phosphorylated (by Akt) binds to a 1433 scaffold protein and translocates to mitochondrial membrane. Can't activate apoptosis here.
