| First Author | Petroulakis E | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 5 | Pages | 439-46 |
| PubMed ID | 19878875 | Mgi Jnum | J:153944 |
| Mgi Id | MGI:4366637 | Doi | 10.1016/j.ccr.2009.09.025 |
| Citation | Petroulakis E, et al. (2009) p53-dependent translational control of senescence and transformation via 4E-BPs. Cancer Cell 16(5):439-46 |
| abstractText | eIF4E, the mRNA 5' cap-binding translation initiation factor, is overexpressed in numerous cancers and is implicated in mechanisms underlying oncogenesis and senescence. 4E-BPs (eIF4E-binding proteins) inhibit eIF4E activity, and thereby act as suppressors of eIF4E-dependent pathways. Here, we show that tumorigenesis is increased in p53 knockout mice that lack 4E-BP1 and 4E-BP2. However, primary fibroblasts lacking 4E-BPs, but expressing p53, undergo premature senescence and resist oncogene-driven transformation. Thus, the p53 status governs 4E-BP-dependent senescence and transformation. Intriguingly, the 4E-BPs engage in senescence via translational control of the p53-stabilizing protein, Gas2. Our data demonstrate a role for 4E-BPs in senescence and tumorigenesis and highlight a p53-mediated mechanism of senescence through a 4E-BP-dependent pathway. |
