BIO 340 FINAL
Card Set Information
BIO 340 FINAL
Cell Cycle Regulation and Cancer
3 checkpoints that detect state of chromosomes (not DNA damage)
1. Intra-S-phase checkpoint
2. Spindle assembly checkpoint
3. Spindle position checkpoint
-point in cell cycle when cell "commits" to entering S phase and completing cell cycle
-happens late in G1 phase
-Before START point, E2F inactive. After START point, E2F is active!
-E2F is a transcription factor. It binds to DNA and causes transcription activation.
-transcribes genes encoding DNA replication and S phase cyclin/Cdks.
-is a "delayed response gene"
-activated by cFos
Mechanism for activation of E2F
1. Mitogen binds to mitogen receptor
2. mitogen receptor is activated and activates Ras
3. Ras triggers MAP kinase cascade
4. MAP kinase cascade leads to transcription/translation of immediate early genes (one gene being Myc)
5.Myc (a regulatory protein) binds to G1-Cdk and activates it indirectly
6. activated G1-Cdk phosphorylates Rb protein
-Rb protein is an inhibitory protein. Before phosphorylation, Rb attaches to E2F and keeps it inactivated. Once phosphorylated, it unbinds from E2F.
7. Rb protein then releases E2F...E2F is now free and active!
Possible changes in E2F activation in Cancer cells
1. Rb is inactivated by another mean (mutant Rb)
-retinoblastoma cancer has a mutant Rb...E2F is always active!
-Rb mutation is a loss of function mutation
2. Ras is always active (mutant Ras)
-phosphorylation of Rb would no longer be dependent on mitogen
-gain of function mutation
-Ras mutation is 2nd most common cause of cancer
3. Gain of function of Myc
-cause of many blood cancers
Gain of function vs Loss of function mutations
-Both lead to deregulated cell division
-Gain of Function
: are promoters. called oncogenes
-Loss of Function
: are tumor suppressor genes