IndraLab
Statements
reach
"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."
reach
"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."
sparser
"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 )."
sparser
"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."
sparser
"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."
reach
"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)."
sparser
"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."
reach
"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]."
rlimsp
"The PI3 kinase/AKT pathway has been shown to increase degradation of the p27 cyclin dependent kinase inhibitor through phosphorylation of consensus AKT sites on p27 and SKP2, and AKT driven proliferation may be checked by feedback mechanisms that increase p27 expression and induce senescence."
sparser
"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."