Bio unit 7 test 4
What causes cancer
failure to respect checkpoints:
- cell division in teh absence of signals
- inappropriate start signals
- failure to induce death of damaged cell
- dividing despite DNA damage
function of cell cycle brakes
- halt/ prevent progression through cell cycle
- P53 detects DNA damage at G1/S checkpoint and leads to the synthesis of inhibitor of G1/S-Cdk and S-Cdk
How is DNA damage recognized and how is cell arrested at G1
1. DNA damage occurs
2. protein kinases phosphorylate P53 stabilizing it and activating it
3. activae P53 binds to regulatory region of P21 gene and initiates transcription to create P21 mRNA
4. translation of P21 mRNA occurs
5. active G1/S - Cdk and S-Cdk are surrounded by P21 (Cdk Inhibitor protein) and are in activated blocking entry to S-phase
Is defective P53 associated with cancer?
- Loss of P53 is found in most cancers
What are the three different Cdk inhibitors and their function
1. P21: surpresses G1/S-Cdk and S-Cdk following DNA damage, transcriptionally regulated by P53
2. P27: supressed G1/S-Cdk and S-Cdk in G1. helps cells withdraw from cell cycle
3. P16: suppresses G1-Cdk, frequently inactivated in cancer cells
What are accelerators
- promote progression is G1->S-phase
- mitogens that activate transcription factors that drive expression of genes that encode proteins for entry into S-phase
What are brakers
- block progression G1->S-phase
- Rb protein binds to/inactivates accelerator transcription factors during G1
- block transcription of stephane genes
what is dysregulation of cell cycle accelerators
- if signal pathway pushing cell cycle gets permanently stuck on, cell division is no longer controlled
what causes dysregulation of cell cycle
- over expression of signals promoting cell cycle
- mutations in signal molecules, their receptors or any molecules in downstream pathways
what is an oncogene (oncoprotein)
- mutated version of normal gene/proteins involved in driving cell diving/proliferation
how does cancer start
- cancer initiates as a failure to respect cell cycle checkpoint, particularily G1/S checkpoint
- once uncontrolled division starts, cells become genetically uncstable (and keep diving despite DNA damage)
- tend to accumulate more and more mutations
- each cancer is caused by a unique combination of errors
what is a proto-oncogene
non mutated version of normal gene/proteins involved in driving cell diving/proliferation