PKC-dependent phosphorylation of p27 at T198 contributes to p27 stabilization and cell cycle arrest

Lapatinib induces p27Kip1-dependent G₁ arrest through both transcriptional and post-translational mechanisms

“…Thr187 and Ser10 are 2 major sites of p27 phosphorylation that regulate p27 subcellular localization, stability, and function in the cells. 47 Lapatinib is able to decrease p27 phosphorylation at Thr187 and increase p27 phosphorylation at Ser10. The process of p27 protein degradation partially depends on phosphorylation at Thr187 by cyclin E/CDK2 complex, which binds to ubiquitin ligase SCF Skp2 , leading to proteasome degradation.…”

K562 cell proliferation is modulated by PLCβ1 through a PKCα-mediated pathway

“…28,29 In detail, cyclin inhibitors such as p21/Cip1 and p27/Kip1, known to be necessary for cell cycle progression, [30][31][32] are often targeted by PKCs. 22,28,29,33 Here, we aimed to investigate the proliferation of Figure 1. overexpression of both pLCβ1 isoforms specifically modulates cyclin D3 protein levels in proliferating K562 cells.…”

Screening of cell cycle fusion proteins to identify kinase signaling networks

“…41 Kip1 and thereby increase protein stability. 41 Consistent with these findings, an algorithm that predicts the www.tandfonline.comprobability that a particular compound will bind a kinase also identified PMA as a likely regulator of PKC. Our data, however, indicate that PMA may also inhibit degradation of other cell cycle proteins, as it also stabilized p21…”

“…Among these, PMA is a compound that is likely to bind PKCa, b, and d. Consistent with this prediction, several studies have shown that PMA potently activates PKCs. 41,50,51 Similarly, kenpaullone and indirubin-3 0 -oxime were predicted to bind GSK3b, on upstream regulator of many cell cycle proteins. Both kenpaullone and indirubin-3 0 -oxime have previously been implicated in interactions with GSK3b and CDKs.…”

“…For instance, phosphorylation at either S10 or T198 has actually been shown to increase the stability of p27 Kip1 . 41,42 In all, 7 phosphorylation sites on the p27 Kip1 protein have been described. These include S10, Y74, Y88, Y89, T157, T187, and T198.…”