Akt-dependent Phosphorylation of p27Kip1Promotes Binding to 14-3-3 and Cytoplasmic Localization

HER2-targeting Antibodies Modulate the Cyclin-dependent Kinase Inhibitor p27Kip1 via Multiple Signaling Pathways

“…Additionally, AKT is reported to be able to phosphorylate p27 Kip1 at Thr198, which also caused the protein to be retained in the cytoplasm. 75 This observation is recently confirmed by another group's data, in which PI3K-AKT signaling is shown to phosphorylate Thr198 and keeps p27 Kip1 in cytosol. 103 It will be interesting to determine the effect of HER2-targeted antibodies on Thr157 and Thr198, because AKT activation correlates well with the expression of p27 Kip1 in the cytosol of patients' breast cancer cells.…”

FOXO transcription factor-dependent p15INK4b and p19INK4d expression

“…In fact, the PI3K inhibitor LY294002 has been observed to induce both G 1 and G 2 /M arrests (Figure 1e; Collado et al, 2000). According to previous studies, LY294002-induced G 1 arrest is considered to be due to activation of p21 CIP1 and p27 KIP1 , whereas G 2 /M arrest by the inhibitor may occur as a result of WEE1Hu activation in addition to p21 CIP1 and p27 KIP1 (Collado et al, 2000;Rodier et al, 2001;Zhou et al, 2001;Fujita et al, 2002;Katayama et al, 2005). Matsushima-Nishiu et al (2001) have shown that adenoviral transduction of the PTEN gene product induces p15 INK4b mRNA expression as same as p27 KIP1 mRNA expression, as seen on DNA microarray and RT-PCR analyses.…”

“…p27 KIP1 is a target of transcription by FOXOs Stahl et al, 2002), and it induces cell-cycle arrest in any phase. In addition, the functions of p21 CIP1 and p27 KIP1 are inhibited by Aktdependent phosphorylation and translocation from nuclei to cytoplasm (Collado et al, 2000;Rodier et al, 2001;Zhou et al, 2001;Fujita et al, 2002). Thus, activation of the Akt signaling pathway can avoid cellcycle arrest of cancer cells.…”

Deregulated degradation of the cdk inhibitor p27 and malignant transformation

“…In particular, the kinase that phosphorylates p27 on Ser-10 and the additional factor(s) necessary for the translocation of p27 from the nucleus to the cytoplasm have not yet been identified. Some recent evidence points to Kis as the kinase responsible for Ser-10 phosphorylation in G1 [71] and to Akt as the additional kinase necessary for p27 nuclear export [72]. However, the kinase phosphorylating p27 on Ser-10 in quiescent cells is still unknown.…”