IndraLab
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"Androgen stimulation also promotes rapid degradation of the cyclin-dependent kinase inhibitor p27. xref xref Our recent data indicate that this p27 degradation is due to androgen stimulation of TORC2, with the subsequent phosphorylation and activation of AKT and phosphorylation of p27 by AKT at a site that enhances p27 degradation (threonine 157). xref The androgen-mediated stimulation of TORC2 appears to be independent of transcription, but its mechanism remains to be determined."
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"In human hepatocellular carcinoma cells, ABT-100 yields growth suppression by decreasing Akt dependent phosphorylation of the cyclin dependent kinase (CDK) inhibitor p27kip1 with concomitant nuclear accumulation of p27kip1, association with CDK2 and resultant inhibition of Cyclin E/CDK2 activity (39)."
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"Since phosphorylation of these cell cycle inhibitors will lead to the cytoplasmic retention of these proteins and precluding their binding and inhibition of the cyclin/CDK complexes, our results suggested that the Akt regulated phosphorylation of p21 and p27 were also involved in the promotion of cell cycle progression from G1 to S/G2M phase in the NaAsO exposed HaCat cells."
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"As KNSTRN activates AKT, which phosphorylates p27 and inhibits its anti-proliferative effect, and the expression of KNSTRN is positively correlated with AKT serine/threonine kinase 1 (AKT1) (Xiong et al. 2021; Huo et al. 2019; Fresno Vara et al. 2004; Hinz and Jücker 2019; Min et al. 2004), we speculate that the inhibitory effect on p27 expression is caused by KNSTRN-mediated activation of AKT."
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"Androgen deprivation also increases levels of the cyclin-dependent kinase inhibitor p27, while androgen stimulation promotes the rapid degradation of p27. xref , xref Recent data indicate that the rapid p27 degradation reflects androgen stimulation of TORC2, the subsequent phosphorylation and activation of AKT, and phosphorylation of p27 by AKT at a site that enhances p27 degradation (threonine 157). xref The androgen-mediated stimulation of TORC2 appears to be independent of transcription, but its mechanism remains to be determined."
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"The PI3K and Akt signaling pathway promotes cell cycle progression through inhibition of GSK-3beta, leading to elevated expression of cyclin D1 and phosphorylated retinoblastoma (pRb), positive G1/S phase cell cycle regulators, and reduced levels of p27, a negative regulator of the G1/S phase of the cell cycle."
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"As KNSTRN activates AKT, which phosphorylates p27 Kip1 and inhibits its anti-proliferative effect, and the expression of KNSTRN is positively correlated with AKT serine/threonine kinase 1 (AKT1) (Xiong et al. xref ; Huo et al. xref ; Fresno Vara et al. xref ; Hinz and Jücker xref ; Min et al. xref ), we speculate that the inhibitory effect on p27 Kip1 expression is caused by KNSTRN-mediated activation of AKT."
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"It has been reported that activated AKT phosphorylates p27 at residues Thr157 and Thr198, induces a phosphorylation-dependent nuclear-cytoplasmic shuttle (out-of-cell nuclear translocation to the cytoplasm) of p27, induces its cytoplasmic redistribution, and impairs its ability to inhibit cell cycle processes (Liang et al., xref ; Shin et al., xref ; Viglietto et al., xref ; Motti et al., xref ), thereby impairing its antiproliferative activity (De Marco et al., xref )."
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"Furthermore, PP2A inhibition with siRNA attenuated apoptotic cell death produced by ceramide, confirming that PP2A plays a role in ceramide induced apoptosis in PC-3 cells.PP2A Regulates p27kip1 Expression Independently of Akt PathwaySince phosphorylation of p27kip1 is an important mechanism that governs p27kip1 inactivation and degradation, it was postulated that PP2A might directly regulate p27kip1 expression by an Akt independent pathway."
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"It has been clarified that Akt phosphorylates P27, weakens nuclear import of P27 kip and opposes P27-mediated G1/S block. xref P27 was widely accepted to be is crucial negative regulator in the G1/S transition by weakening CDK2. xref Besides cyclin/CDK kinase activity mediation, P27 was also involved in cytoskeletal dynamics, cell motility and cell invasion."
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"Transient C-terminal p27 phosphorylation by pAKT in early G1 delays nuclear p27 import ( xref ) and promotes cyclin D-CDK4/6 assembly and activation ( xref , xref , xref ) as Src and cyclin E-Cdk2 phosphorylate p27 to mediate its proteolysis and promote G1 transit ( xref , xref )."
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"TM4SF5 expression also causes overexpression of p27 Kip1, although how it occurs is unknown; TM4SF5 causes Akt mediated Ser10 phosphorylation of p27 Kip1, leading to its stabilization, RhoA activity changes, and eventually morphological elongation for the EMT and contact inhibition loss [XREF_BIBR]."
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"AKT promotes cell survival and growth by phosphorylating the pro apoptotic protein Bad (which results in inactivation of Bad), the transcriptional regulator FoxO (which results in activation of FoxO), and the cyclin dependent kinase inhibitor p27 (which results in activation of p27)."
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"The cell cycle protein p27 is downstream of Akt and AMPK. xref – xref Reduced p27 correlates with ErbB2/Neu overexpression, resistance, and poor clinical outcome. xref – xref Moreover, increased p27 expression has been shown to increase sensitivity to trastuzumab in resistant HER2+ breast cancer cells. xref Akt directly phosphorylates p27 on multiple Threonine (T) residues, including T198, which have been shown to promote nuclear export and sequestration of p27 in the cytoplasm, resulting in the inactivation of the protein in human cells."
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"In human hepatocellular carcinoma cells, ABT-100 yields growth suppression by decreasing Akt-dependent phosphorylation of the cyclin dependent kinase (CDK) inhibitor p27kip1 with concomitant nuclear accumulation of p27kip1, association with CDK2 and resultant inhibition of Cyclin E/CDK2 activity (39)."
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"The physiological sig-nificance of the interactions of p27 with Grb2 and 14-3-3 arenot well understood, but AKT phosphorylation of p27 allows itsbinding to 14-3-3 which helps limit the nuclear compartmentalization of p27.25 Another non canonical process of cellular regu lation by p27 was suggested by Besson et al, who demonstratedthat p27, independently of its CDK inhibitory activity, functioned as a dominant oncogene in vivo, promoting stem-cell expansion and spontaneous multi-organ tumorigenesis.29 Inaddition, other non canonical cell control mechanisms have been described for nuclear localized p27."