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CDK2 phosphorylates NPM1. 33 / 34
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"However, loss of mouse RABL6A greatly increased Cdk2-dependent phosphorylation of GST-NPM in vitro , which was prevented by human RABL6A expression ( xref )."
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"Phosphorylation of nucleophosmin by Cdk2 and cyclin E results in nucleophosmin 's removal from the centrosome, coinciding with initiation of procentriole formation."
19277494
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"XREF_BIBR We found that AKAP350CTD expression induced an increase in Cdk2 specific phosphorylation of NPM, indicating that AKAP350 enables Cdk2 centrosomal activity at the G 1 / S transition."
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"For example, Cdk2 phosphorylates NPM and B23 (Nucleophosmin) XREF_BIBR on threonine (T) 199 resulting in its dissociation from the centrosome prior to the initiation of centriole duplication XREF_BIBR."
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"These results suggest that NPM and B23 phosphorylated by CDK2 and cyclin E dissociates from centrosomes."
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"CDK2 phosphorylates nucleophosmin (NPM/B23), enabling Mps1 to localize to the centrosome, which seems to be a critical step in procentriole formation, as the removal of NPM/B23 and/or Mps1 causes centriole re-duplication [ xref , xref ]."
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"For determining the specificity of the Cdk2-dependent phosphorylation of nucleophosmin, GST-NPM/wt and GST-NPM/T199A (thr199 is replaced by ala) were subjected to in vitro kinase reaction with Cdk2/cy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It is not known whether nucleophosmin can also be phosphorylated by the Cdk2 and cyclin A complex."
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"In this regard, PKA participates in the separation of the centrioles by phosphorylating its structural component centrin. xref It is probable that AKAP350 integrates different events involved in the initiation of centrosomal duplication, such as phosphorylation of centrin by PKA, and phosphorylation of NPM by Cdk2."
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"Thus, binding of anti-NPM and B23 antibody blocks CDK2 and cyclin E mediated phosphorylation of NPM and B23."
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"In addition to NPM’s phosphorylation by cyclin E–cdk2, its nuclear export by the Ran–Crm1 complex has also been implicated in NPM’s induction of centrosome duplication."
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"Although NPM1 is phosphorylated by the G1/S checkpoint regulator cdk2 XREF_BIBR, it was not clear if NPM1 could also serve as a cdk1 substrate for centriole disjunction during S-phase XREF_BIBR XREF_BIBR."
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"We show that centriole duplication is blocked when nuclei were preincubated with the anti-NPM and B23 antibody that prevents phosphorylation of NPM and B23 by CDK2 and cyclin E."
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"Accordingly, the expression of this AKAP350 domain increased the endogenous phosphorylation of nucleophosmin by Cdk2, which occurs at the G1/S transition and is a marker of the centrosomal activity of the cyclin E-Cdk2 complex."
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"As one example, activated E-CDK2 kinase phosphorylates nucleophosmin (NPM/B23) to ensure proper centrosome duplication."
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"As phosphorylation of human NPM by cyclin E–cdk2 was reported to be essential for the initiation of centrosome duplication in late G 1 ( xref ), we considered that ARF might inhibit NPM phosphorylation in addition to retaining it in the nucleolus to arrest cell growth before S-phase entry ( xref )."
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"Since HBx is reported to potentiate the activity of CDK2 kinase [41] which phosphorylates NPM at Thr 199 [55], we next monitored the phosphorylation status of NPM in its presence."
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"While RABL6A silencing enhanced Cdk2 mediated phosphorylation of NPM, it had no impact on Cdk2 activity toward histone H1."
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"Cdk2-cyclin E phosphorylates nucleophosmin on isolated centrosomes , causing it to be dissociated from the centrosomes."
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"It has been shown recently that cdk2 and cyclin-E-mediated phosphorylation of nucleophosmin and B23 can function as a licensing factor for centrosome duplication [13]."
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"The cdk2 and cyclin E complex phosphorylates nucleophosmin and B23, which associates specifically with unduplicated centrosomes and may be involved in initiating centrosome duplication [36]."
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"However, loss of mouse RABL6A greatly increased Cdk2 dependent phosphorylation of GST-NPM in vitro, which was prevented by human RABL6A expression (XREF_FIG)."
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"XREF_BIBR It is probable that AKAP350 integrates different events involved in the initiation of centrosomal duplication, such as phosphorylation of centrin by PKA, and phosphorylation of NPM by Cdk2."
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"It interacts with cyclin dependent kinase 2 (Cdk2) to phosphorylate the target genes nuclear protein ataxia-telangiectasia locus (NPAT) and nucleophosmin, critical components of cell proliferation and DNA replication, respectively [XREF_BIBR]."
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"XREF_BIBR We analyzed NPM phosphorylation at its specific Cdk2 site, and found that the expression of AKAP350CTD induced an increase in NPM phosphorylation by Cdk2 (XREF_FIG)."
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"At late G 1 phase, NPM is phosphorylated by cyclin E-Cdk2, phosphorylation which induces NPM release from the centrosomes and the initiation of centrosomal duplication. xref We found that AKAP350CTD expression induced an increase in Cdk2 specific phosphorylation of NPM, indicating that AKAP350 enables Cdk2 centrosomal activity at the G 1 /S transition."
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"The phosphorylation of NPM1 by CDK2 and Cyclin E promotes the release of NPM1 from the centrosome during duplication; this represents an essential step for duplication to occur."
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"In transactivation activity dependent mechanism, p21 expression plays a key role in synchronizing DNA replication and centrosome duplication by inhibiting Cdk2 and Cyclin E activity which phosphorylates Nucleophosmin and NPM1 at centrosomes to promote its dissociation from the centrosomes to allow initiation of centrosome duplication."
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"Cdk2 and Cdk4 were proposed to promote centriole reduplication in mouse fibroblasts by hyperphosphorylating the centrosomal protein nucleophosmin, a putative inhibitor of centriole duplication."
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"Accordingly, the expression of this AKAP350 domain increased the endogenous phosphorylation of nucleophosmin by Cdk2, which occurs at the G 1 /S transition and is a marker of the centrosomal activity of the cyclin E-Cdk2 complex."
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"Cdk2 activity is also synchronised with these events, as cyclin E1-Cdk2 phosphorylates nucleophosmin, CP110 and Mps1, promoting centrosome duplication [ xref , xref , xref ]."
20180967
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"Accordingly, the expression of this AKAP350 domain increased the endogenous phosphorylation of nucleophosmin by Cdk2, which occurs at the G 1 / S transition and is a marker of the centrosomal activity of the cyclin E and Cdk2 complex."
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"GST-NPM and B23 preincubated with either anti-gag (lane 2) or anti-myc (lane 3) antibody was phosphorylated by CDK2 and cyclin E at similar levels with the control with no antibody (lane 1)."
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