BIO 340 FINAL

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

• 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!

• 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

• -Both lead to deregulated cell division
• -Gain of Function: are promoters. called oncogenes
• -Loss of Function: are tumor suppressor genes