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- _5 value "from full text - Box 2 | Bcl2 and the Rb/Arf/p53 network Inactivation of the retinoblastoma (Rb) pathway ? for example, by loss of cell-cycle inhibitor Ink4a, which can prevent cyclin-D?Cdk4 from phosphorylating Rb ? unleashes the transcription factor E2f1,which increases expression of Arf, a protein that is encoded by the same locus as Ink4a (REF. 136).Arf,which is also a transcriptional target of Myc, sequesters Mdm2, a negative regulator of p53. Raised p53 levels can either impose growth arrest, typically by inducing the Waf1 cell-cycle inhibitor, or promote apoptosis through targets such as Bax, Puma and Noxa. The apoptotic targets seem to also require the p53 relative p63 or p73 (REF. 152). Circles/ovals denote oncogene products; rectangles denote known or likely tumour suppressors. For more detail, see REFS 4?6,136.ATM, ataxia telengiectasia mutated; Chk2, checkpoint 2; NF-?B, nuclear factor-?B." provenance.
- _5 wasQuotedFrom 12209154 provenance.