Identification of a polymorphism in the RING finger of human Bmi-1 that causes its degradation by the ubiquitin–proteasome system

Zhang, Jie; Sarge, Kevin D.

doi:10.1016/j.febslet.2009.02.023

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Volume 583, Issue 6 , Pages 960-964, 18 March 2009

Identification of a polymorphism in the RING finger of human Bmi-1 that causes its degradation by the ubiquitin–proteasome system

Edited by Zhijie Chang

Graduate Center for Toxicology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, United States

Department of Molecular and Cellular Biochemistry, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, United States

Received 12 December 2008; received in revised form 11 February 2009; accepted 15 February 2009. published online 24 February 2009.

Abstract

Bmi-1 is a polycomb protein that plays an important role in tumor cell development and maintaining stem cell populations of many cell lineages. Here we identify a polymorphism in human Bmi-1 that changes a cysteine within its RING domain to tyrosine. This C18Y polymorphism is associated with a significant decrease in Bmi-1 level and its elevated ubiquitination, suggesting that it is being destroyed by the ubiquitin–proteasome system. Consistent with this, treating cells with the proteasome inhibitor MG-132 significantly increases C18Y Bmi-1 levels. This is the first example of a polymorphism in Bmi-1 that reduces levels of this important protein.

Structured summary

MINT-6948574: Bmi-1 (uniprotkb:P35226) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007)

Keywords: Bmi-1, RING finger, Ubiquitin, Proteasome, Degradation