Effects of MdmX on Mdm2-mediated downregulation of pRB

FEBS Letters
Chiharu UchidaMasatoshi Kitagawa

Abstract

Mdm2, a RING-finger type ubiquitin ligase, is overexpressed in a variety of human cancers. It promotes ubiquitination of the tumor suppressor p53 and can function as an oncogene by largely downregulating p53. Recently, we reported that Mdm2 degrades retinoblastoma tumor suppressor protein (pRB) via the ubiquitin-proteasome system. In the present study, we assessed the effects of MdmX, a structural homolog of Mdm2, on the Mdm2-mediated ubiquitination of pRB. MdmX is known to negatively regulate p53 function by enhancing the Mdm2-mediated ubiquitination and degradation of p53. Interestingly, MdmX inhibited the Mdm2-mediated pRB ubiquitination. Furthermore, an MdmX siRNA decreased the endogenous pRB level, while MdmX overexpression stimulated pRB functions in cultured cells. Therefore, MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53.

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Citations

Jul 31, 2007·Pharmacology & Therapeutics·Christian BronnerValérie B Schini-Kerth
May 23, 2009·Cancer Science·Kyoko KitagawaMasatoshi Kitagawa
Mar 14, 2007·International Journal of Cancer. Journal International Du Cancer·Christoph R MüllerOla Myklebost
Dec 20, 2011·Pediatric Blood & Cancer·Adriana Helena de Oliveira ReisFernando Regla Vargas
Sep 1, 2015·Biochimica Et Biophysica Acta·Satyaki Sengupta, R William Henry
Jan 5, 2017·Genes & Cancer·Jesús Hernández-MongeVanesa Olivares-Illana
Jul 3, 2016·Cold Spring Harbor Perspectives in Medicine·Jean-Christophe Marine, Aart G Jochemsen
Jan 20, 2017·BioMed Research International·Chiharu Uchida
Aug 28, 2020·Frontiers in Oncology·De-Hua YuJiang-Jiang Qin

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