First Author | Prince S | Year | 2004 |
Journal | Cancer Res | Volume | 64 |
Issue | 5 | Pages | 1669-74 |
PubMed ID | 14996726 | Mgi Jnum | J:88831 |
Mgi Id | MGI:3037248 | Doi | 10.1158/0008-5472.can-03-3286 |
Citation | Prince S, et al. (2004) Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor. Cancer Res 64(5):1669-74 |
abstractText | T-box factors play a crucial role in the development of many tissues, and mutations in T-box factor genes have been implicated in multiple human disorders. Some T-box factors have been implicated in cancer; for example, Tbx2 and Tbx3 can suppress replicative senescence, whereas Tbx3 can cooperate with Myc and Ras in cellular transformation. The p21(WAF1) cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development. |