Polo-like kinase-1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated p53 turnover

0Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

Abstract

The E3 ubiqutin ligase, murne double-minute clone 2 (MDM2), promotes the degradation of p53 under normal homeostatic conditions. Several serine residues within the acidic domain of MDM2 are phosphorylated to maintain its activity but become hypo-phosphorylated following DNA damage, leading to inactivation of MDM2 and induction of p53. However, the signalling pathways that mediate these phosphorylation events are not fully understood. Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (PLK1), phosphorylates MDM2 at one of these residues, Ser260, and stimulates MDM2-mediated turnover of p53. These data are consistent with the idea that deregulation of PLK1 during tumourigenesis may help suppress p53 function. Structured summary: MINT-7266353: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by pull down (MI:0096). MINT-7266344, MINT-7266329: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by anti bait coimmunoprecipitation (MI:0006). MINT-7266250: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) p53 (uniprotkb:P04637) by protein kinase assay (MI:0424). MINT-7266241, MINT-7266318: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:P23804) by protein kinase assay (MI:0424). MINT-7266231, MINT-7266805, MINT-7266264, MINT-7266299: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:Q00987) by protein kinase assay (MI:0424). © 2009.

Cite

CITATION STYLE

APA

Dias, S. S., Hogan, C., Ochocka, A. M., & Meek, D. W. (2009). Polo-like kinase-1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated p53 turnover. FEBS Letters, 583(22), 3543–3548. https://doi.org/10.1016/j.febslet.2009.09.057

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free