| First Author | Cecchini MJ | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 11 | Pages | 2029-45 |
| PubMed ID | 24662053 | Mgi Jnum | J:215358 |
| Mgi Id | MGI:5605152 | Doi | 10.1128/MCB.01589-13 |
| Citation | Cecchini MJ, et al. (2014) A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene-targeted mice. Mol Cell Biol 34(11):2029-45 |
| abstractText | The retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report, we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1(DeltaG)) are defective for pRB-dependent repression of E2F target genes. Except for an accelerated entry into S phase in response to serum stimulation, cell cycle regulation in Rb1(DeltaG/DeltaG) mouse embryonic fibroblasts (MEFs) strongly resembles that of the wild type. In a serum deprivation-induced cell cycle exit, Rb1(DeltaG/DeltaG) MEFs display a magnitude of E2F target gene derepression similar to that of Rb1(-/-) cells, even though Rb1(DeltaG/DeltaG) cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1(DeltaG/DeltaG) MEFs is responsive to p16 expression and gamma irradiation, indicating that alternate mechanisms can be activated in G1 to arrest proliferation. Some Rb1(DeltaG/DeltaG) mice die neonatally with a muscle degeneration phenotype, while the others live a normal life span with no evidence of spontaneous tumor formation. Most tissues appear histologically normal while being accompanied by derepression of pRB-regulated E2F targets. This suggests that non-E2F-, pRB-dependent pathways may have a more relevant role in proliferative control than previously identified. |
