IndraLab
Statements
reach
"While phosphorylation on Thr187 by Cdk2 and cyclin E complexes is essential for its ubiquitination and degradation, p27 is also phosphorylated by PKB and AKT on Thr157 in HCC, inducing its relocalization to the cytoplasm and impairing its negative effect on nuclear Cdk and cyclin complexes (XREF_FIG) [XREF_BIBR, XREF_BIBR]."
reach
"Noting that the growth inhibitory (nuclear) function of p27 is required for EGFR-TKI efficacy, IGF1R activation causes resistance to EGFR-TKIs, the IGF1R is a potent activator of Akt, and Akt phosphorylates p27 at T157 with resultant cytoplasmic sequestration of p27 and cell cycle progression, we evaluated regulation of p27 by EGFR-TKIs in an OSCC cell line in the presence or absence of simultaneous IGF1R activation."
"It is known that Akt phosphorylates Thr 157 of p27 and this reduces the nuclear import activity of p27. Using a pull-down experiment, 14-3-3 was identified as the Thr157-phosphorylated p27NLS-binding protein Although importin alpha5 bound to Thr157-phosphorylated p27NLS, 14-3-3 competed with importin alpha5 for binding to it. Thus, 14-3-3 sequestered phosphorylated p27NLS from importin alpha binding, resulting in cytoplasmic localization of NLS-phosphorylated p27. "
reach
"Akt modulated the activity of p21Cip1 by influencing the phosphorylation level and the binding with PCNA to increase cell proliferaion; XREF_BIBR Akt could also directly phosphorylate p27Kip1 at Thr157 resulting in p27Kip1 retention in the cytoplasm, preventing cell cycle blockade mediated by p27Kip1."
sparser
"Noting that ( xref ) the growth inhibitory (nuclear) function of p27 is required for EGFR-TKI efficacy, ( xref ) IGF1R activation causes resistance to EGFR-TKIs, ( xref ) the IGF1R is a potent activator of Akt, and ( xref ) Akt phosphorylates p27 at T157 with resultant cytoplasmic sequestration of p27 and cell cycle progression, we evaluated regulation of p27 by EGFR-TKIs in an OSCC cell line in the presence or absence of simultaneous IGF1R activation."
reach
"While phosphorylation on Thr187 by Cdk2 and cyclin E complexes is essential for its ubiquitination and degradation, p27 is also phosphorylated by PKB and AKT on Thr157 in HCC, inducing its relocalization to the cytoplasm and impairing its negative effect on nuclear Cdk and cyclin complexes (XREF_FIG) [XREF_BIBR, XREF_BIBR]."
reach
"In the early G1 phase, Thr157 and Thr198 of p27 are phosphorylated by Akt, p90RSK1 (p90 ribosomal protein S6 kinases), SGK (serum and glucocorticoid‐inducible kinase), AMPK and PIM (although this phosphorylation is relatively rare), which will prevent the nuclear transfer of p27 .62 Moreover, Akt induces phosphorylation of Thr157 and Thr198 to form a recognition motif for 14‐3‐3 protein to prevent nuclear translocation of p27 .63 Thus, Akt might also implicate in the nuclear and cytoplasmic distribution of p27 ."
sparser
"Akt modulated the activity of p21Cip1 by influencing the phosphorylation level and the binding with PCNA to increase cell proliferaion; xref Akt could also directly phosphorylate p27Kip1 at Thr157 resulting in p27Kip1 retention in the cytoplasm, preventing cell cycle blockade mediated by p27Kip1. xref However, in this study, we have not found a difference in O -GlcNAcylation-induced proliferation by Akt activation in thyroid anaplastic cancer 8305C cells."
reach
"It has been suggested that the cell cycle inhibitors, p21 and p27, could be phosphorylated at Thr 145 and Thr 157, respectively, by Akt, which will lead to cytoplasmic retention of both of the proteins and finally prevent their binding and inhibition of the cyclin/CDK complexes (Cheung and Testa, 2013)."
rlimsp
"Cytoplasmic localization of p27 correlated with phosphorylation at T157, an AKT phosphorylation site in the p27 NLS. In RCC cell lines, activated PI3K/AKT signaling was accompanied by mislocalization of p27. AKT activation and phosphorylation of p27 was associated with resistance to apoptosis, and small interfering RNA knockdown of p27 or relocalization to the nucleus increased apoptosis in RCC cells. Treatment with the PI3K inhibitors LY294002 or wortmannin resulted in nuclear relocalization of p27, whereas mTOR inhibition by rapamycin did not. CONCLUSIONS: In RCC, p27 is phosphorylated at T157 of the NLS, with increasing tumor grade associated with cytoplasmic p27."
sparser
"In the early G1 phase, Thr157 and Thr198 of p27 Kip1 are phosphorylated by Akt, p90RSK1 (p90 ribosomal protein S6 kinases), SGK (serum and glucocorticoid‐inducible kinase), AMPK and PIM (although this phosphorylation is relatively rare), which will prevent the nuclear transfer of p27 Kip1 . xref Moreover, Akt induces phosphorylation of Thr157 and Thr198 to form a recognition motif for 14‐3‐3 protein to prevent nuclear translocation of p27 Kip1 . xref Thus, Akt might also implicate in the nuclear and cytoplasmic distribution of p27 Kip1 ."
sparser
"However, p27 levels are known to be elevated in many tumor types, a paradox that was resolved by independent reports that in tumors with elevated levels of p27, pro-growth signaling results in activation of Akt, that phosphorylates p27 at threonine 157 (T157) ( xref ), thereby interfering with its import into the nucleus [ xref – xref ]."