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Publication : CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S progression.

First Author  Liu F Year  2006
Journal  Mol Cell Biol Volume  26
Issue  8 Pages  3124-34
PubMed ID  16581787 Mgi Jnum  J:107424
Mgi Id  MGI:3621112 Doi  10.1128/MCB.26.8.3124-3134.2006
Citation  Liu F, et al. (2006) CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S progression. Mol Cell Biol 26(8):3124-34
abstractText  Cell cycle progression from G(1) to S phase is mainly controlled by E2F transcription factors and RB family proteins. Previously we showed that the presence of CtIP is essential for G(1)/S transition in primary mouse blastocysts, as well as in NIH 3T3 cells. However, how CtIP executes this function remains to be elucidated. Here we show that in NIH 3T3 cells the expression of CtIP is regulated by the E2F/RB pathway during late G(1) and S phases. The presence of wild-type CtIP, but not the E157K mutant form, which failed to interact with RB, enhanced its own promoter activity. Chromatin immunoprecipitation analysis indicated that the recruitment of CtIP to its promoter occurs concomitantly with TFIIB, a component of the RNA polymerase II complex, and with dissociation of RB from the promoter during late G(1) and G(1)/S transition. Similar positive regulation of cyclin D1 expression by CtIP was also observed. Consistently, cells expressing the CtIP(E157K) protein alone exhibited growth retardation, an increase in the G(1) population, and a decrease in the S-phase population. Taken together, these results suggest that, contrary to the postulated universal corepressor role, CtIP activates a subset of E2F-responsive promoters by releasing RB-imposed repression and therefore promotes G(1)/S progression.
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