First Author | Sim KG | Year | 2006 |
Journal | Cell Cycle | Volume | 5 |
Issue | 10 | Pages | 1111-5 |
PubMed ID | 16721052 | Mgi Jnum | J:196054 |
Mgi Id | MGI:5486445 | Doi | 10.4161/cc.5.10.2797 |
Citation | Sim KG, et al. (2006) The TRIP-Br family of transcriptional regulators is essential for the execution of cyclin E-mediated cell cycle progression. Cell Cycle 5(10):1111-5 |
abstractText | The G1 D-type cyclins, in conjunction with cyclin-dependent kinases Cdk4 and Cdk6, play key roles in the execution of mitogen-induced cellular proliferation. TRIP-Br1, a member of the TRIP-Br family of transcriptional regulators, has been implicated in the regulation of Cdk4/cyclin D activity. To further elucidate the functional role(s) of the TRIP-Br proteins in mitogenic signaling, we have developed the synthetic DNA enzymes E-Br1 and E-Br2 to specifically knock down the serum-inducible expression of TRIP-Br1 and TRIP-Br2, respectively, in WI-38 human fibroblasts in culture, as well as generated TRIP-Br2 null primary embryonic fibroblasts from a novel TRIP-Br2 knockout mouse model. Both strategies consistently reveal that ablation of TRIP-Br1 or TRIP-Br2 expression disrupts mitogenic signaling in a manner that suppresses serum-induced cyclin E expression, S-phase entry and cellular proliferation. We conclude that both TRIP-Br1 and TRIP-Br2 are required for proper transduction of mitogenic signals and execution of serum-inducible cell cycle progression. |