IndraLab

"Although the receptor-selective retinoids induce minimal amounts of apoptosis in T47D breast cancer cells, the predominant factor that leads to growth arrest is G1 cell cycle blockade. Our data indicate that this blockade results from the downregulation of Cyclin D1 and Cyclin D3, which in turn causes Rb hypophosphorylation."

"<E7> E2F-DP dimers, complexed with pRb, p107, or p130, can bind and inhibit E2 promoter elements (Dyson, 1998; Mayol and Grana, 1998). In quiescent cells, the predominant complexes contain E2F4 and p130. E2F1_DP:RB1-|taof(E2F1_DP) E2F2_DP:RB1-|taof(E2F2_DP) E2F3_DP:RB1-|taof(E2F3_DP) E2F4_DP:RB1-|taof(E2F4_DP) E2F1_DP:RBL1-|taof(E2F1_DP) E2F2_DP:RBL1-|taof(E2F2_DP) E2F3_DP:RBL1-|taof(E2F3_DP) E2F4_DP:RBL1-|taof(E2F4_DP) E2F1_DP:NOLC1-|taof(E2F1_DP) E2F2_DP:NOLC1-|taof(E2F2_DP) E2F3_DP:NOLC1-|taof(E2F3_DP) E2F4_DP:NOLC1-|taof(E2F4_DP)"

"The sensitivity of the Rb phosphatase in intact cells to various cell-permeable cytotoxins also points to PP1 (396). D. Exit From the Pachytene Stage in Yeast Meiosis In yeast, a premature exit from the pachytene stage after the initiation of meiotic recombination is prevented by the so-called \"pachytene checkpoint\" (reviewed in Ref. 303). An active checkpoint results in the phosphorylation and activation of protein kinase Mek1, which keeps its substrate Red1 phosphorylated (29, 102). When recombination has ended in late pachytene, the checkpoint is inactivated by the dephosphorylation of Red1 by PP1 (30). Overexpression of PP1 bypasses the checkpoint precociously. The nature of the regulatory subunit(s) associated with this meiotic function of PP1 remains unclear. A number of findings originally pointed to Gip1, a PP1- binding protein that is specifically expressed in middle meiosis and that is essential for sporulation (372). Thus it was reported that 1) Gip1 was required for the targetting of PP1 to chromosomes in late pachytene, 2) yeast cells lacking Gip1 displayed a pachytene arrest that was similar to that of cells with constitutively active Mek1 or with a deficient version of PP1, and 3) this arrest was alleviated by overexpression of PP1 (30). However, in a more recent study, deletion of the Gip1-encoding gene was found not to affect meiotic progression, but instead to interfere with the normal localization of sporulation-specific septins and the deposition of spore wall material (347). Strikingly, replacement of PP1 by a mutant version that fails to interact with Gip1 yielded a similar phenotype. IV. CELL CYCLE ARREST AND APOPTOSIS PP1 not only activates the Rb protein at the M/G1 transition (see sect. IIIC), but it is also implicated in the control of Rb at the G1/S transition and in Rb-mediated cell cycle arrest."

"Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation"

"GCIP, a newly identified cyclin D-interacting protein, was found to reduce the phosphorylation of retinoblastoma protein and inhibit E2F1-mediated transcriptional activity."

"We found that Id-1 expression induced phosphorylation of RB and down-regulation of p16(INK4a) but not p21(Waf1)or p27(Kip1)"