Regulation of p53 level by UBE4B in breast cancer

Ying Zhang; Yanrong Lv; Yongyang Zhang; Haidong Gao

doi:10.1371/journal.pone.0090154

Regulation of p53 level by UBE4B in breast cancer

PLoS One. 2014 Feb 26;9(2):e90154. doi: 10.1371/journal.pone.0090154. eCollection 2014.

Authors

Ying Zhang¹, Yanrong Lv¹, Yongyang Zhang², Haidong Gao¹

Affiliations

¹ Department of Breast Surgery, QiLu Hospital, Jinan, China.
² Emergency Department, Shandong Jining No.1 People's Hospital, Jining, China.

Abstract

p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Biomarkers, Tumor / metabolism
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Carcinogenesis
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Proteolysis
Proto-Oncogene Proteins c-mdm2 / metabolism
Tumor Suppressor Protein p53 / metabolism*
Tumor Suppressor Proteins / metabolism*
Ubiquitin-Protein Ligase Complexes / metabolism*
Ubiquitin-Protein Ligases
Ubiquitination

Substances

Biomarkers, Tumor
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
Ubiquitin-Protein Ligase Complexes
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2
UBE4B protein, human
Ubiquitin-Protein Ligases

Grants and funding

The source of funding that has supported this work is the Nature Science of Shandong Province, ZR2009CM007, ZR2010HM131 (http://www.sdnsf.gov.cn/portal/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.