rb tumor suppressor/checkpoint signaling in response to dna damage
| PAG Title | rb tumor suppressor/checkpoint signaling in response to dna damage |
| PAG ID | WAG001032 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | Cell cycle checkpoint controls at the G1 to S transition and the G2 to M transition prevent the cell cycle from progressing when D is damaged. The ATM protein kise detects D damage and in response to this activates D repair factors and inhibits cell cycle progression. Two of the proteins that ATM phosphorylates in response to D damage are the tumor suppressor p53 and the checkpoint kise chk1. In turn, the tumor suppressor p53 interacts with p21 to block the activity of cdk2 (cyclin dependent kise 2) preventing passage from G1 to S phase and harmful replication of damaged D. One of the targets of cdk2 is the Rb gene product, another tumor suppressor. When dephosphorylated, Rb interacts with E2F transcription factors and prevents transcription of genes required for progression through the cell cycle. When phosphorylated by cell cycle dependent kises like cdk2 and cdk4, Rb no longer interacts with E2F and the cell cycle proceeds through the G1-S checkpoint (see 'Cyclins and Cell Cycle Regulation' pathway and 'Cell Cycle: G1/S Check Point' pathway). D damage also regulates the G2-M phase transition by acting on the cell cycle regulator cdc2 (See 'cdc25 and chk1 Regulatory Pathway in response to D damage'). |
| Species | Homo sapiens |
| nCoCo Score | 1,484 |
| Base PAG ID | WAG001032 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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