IndraLab

Statements

NPM1 is phosphorylated on S48. 19 / 19
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rlimsp
"(E) Ribbon diagram of the NPM pentameric ring (top view) showing a space filling model of phosphorylation at Ser48, highlighting a steric clash with the neighbouring subunit."
25071014
sparser
"AKT interacts with NPM, resulting in NPM phosphorylation at serine 48 (located in the oligomerization domain)."
32759846
sparser
"In the presence of myr-AKT1, we observed an increased monomeric NPM fraction, corresponding with increased NPM-S48 phosphorylation, implying that phosphorylation prevents NPM oligomers in a Ser48 dependent manner (Fig. xref , lanes 4-6)."
25071014
sparser
"This suggests that phosphorylation of NPM-Ser48 is a physiological signal that directs NPM localization via the regulation of NPM oligomerisation."
25071014
sparser
"Since phosphorylation of NPM-Ser48 appears to dictate both NPM oligomerisation and localization, we wished to address whether this mechanism may also affect NPM interacting proteins that are functionally controlled by trafficking to and from the nucleolus [ xref ]."
25071014
rlimsp
"Besides, AKT-mediated phosphorylation of NPM-Ser48 can prevent the oligomerization of NPM1, and subsequently results in nucleoplasmic localization of p14ARF, constitutive HDM2 inhibition and stabilization of p53."
26119940
sparser
"In T24 cells, where NPM is phosphorylated on Ser48 (Fig. xref ), inhibition of AKT decreases the monomeric fraction of NPM ( xref ) and increases NPM oligomers ( xref )."
25071014
sparser
"These results suggest that AKT mediated phosphorylation of NPM-Ser48 promotes cellular resistance to IR by promoting ARF relocalization to the nucleoplasm and the stabilization of p53 mut ."
25071014
sparser
"NPM1 phosphorylation at Ser48 by prosurvival kinase Akt led to NPM1 pentamer disassembly and exit from the nucleolus 7 , and so not surprisingly NPM1 phosphorylated at Ser48 is prevalent in human tumo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38702038
sparser
"Having established that the phosphorylation of NPM-Ser48 by AKT promotes ARF nucleoplasmic localization, MDM2 inhibition and the stabilization of p53 mut , we next wished to address if phosphorylation of NPM-Ser48 was a common phenomenon, and potentially contributing to the stabilization of p53 mut in human tumors."
25071014
rlimsp
"We interpret this as an inability of AKT to target oligomeric NPM due to Ser48 inaccessibility in the pentameric ring, but also that the cycling pool of NPM can be phosphorylated and prevented from forming pentamers, which prevents NPM:ARF sequestration rather than disrupting localization."
25071014
rlimsp
"In T24 cells, where NPM is phosphorylated on Ser48 (Fig. 1D), inhibition of AKT decreases the monomeric fraction of NPM (Fig."
25071014
rlimsp
"In the presence of myr-AKT1, we observed an increased monomeric NPM fraction, corresponding with increased NPM-S48 phosphorylation, implying that phosphorylation prevents NPM oligomers in a Ser48 dependent manner (Fig. 1F, lanes 4-6)."
25071014
rlimsp
"Thus, oncogenic activation of AKT disrupts NPM quaternary dynamics via phosphorylation of Ser48."
25071014
rlimsp
"To address if phosphorylation of NPM-S48 regulated NPM oligomerisation, Npm; p53 MEF (hereafter Npm−/− MEF) were reconstituted with NPM-WT, non-phosphorylatable NPM-S48A or phosphomimetic NPM-S48E derivatives (Fig. 1F and S1G) and lysates from reconstituted Npm MEF were resolved under native conditions."
25071014
rlimsp
"Since phosphorylation of NPM-Ser48 appears to dictate both NPM oligomerisation and localization, we wished to address whether this mechanism may also affect NPM interacting proteins that are functionally controlled by trafficking to and from the nucleolus [36]."
25071014
sparser
"Together our biochemical data indicated that Ser48 phosphorylation of NPM1 drove its interaction with 14-3-3ζ, securing the formation of the 14-3-3/NPM1 phosphopeptide interface."
36041327
sparser
"NPM1 phosphorylation at Ser48 by prosurvival kinase Akt led to NPM1 pentamer disassembly and exit from the nucleolus [ xref ], and so not surprisingly NPM1 phosphorylated at Ser48 is prevalent in human tumors [ xref ]."
38405961
sparser
"It has been reported that ATM-mediated phosphorylation of NPM1 can inhibit the binding of NPM1 with p14ARF, and thereby promoting the translocation of p14ARF to nucleoplasm. xref , xref Besides, AKT-mediated phosphorylation of NPM-Ser48 can prevent the oligomerization of NPM1, and subsequently results in nucleoplasmic localization of p14ARF, constitutive HDM2 inhibition and stabilization of p53. xref However, we observed no effect of SOX6 on the phosphorylation of NPM1."
26119940