DBC1 Functions as a Tumor Suppressor by Regulating p53 Stability

被引：75

作者：

Qin, Bo ^{[1
,2
]}

Minter-Dykhouse, Katherine ^{[3
]}

Yu, Jia ^{[3
]}

Zhang, Jun ^{[4
]}

Liu, Tongzheng ^{[2
]}

Zhang, Haoxing ^{[2
]}

Lee, SeungBaek ^{[2
]}

Kim, JungJin ^{[2
]}

Wang, Liewei ^{[3
]}

Lou, Zhenkun ^{[2
]}

机构：

[1] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China

[2] Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA

[4] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

来源：

CELL REPORTS | 2015年 / 10卷 / 08期

关键词：

POSTTRANSLATIONAL MODIFICATION; POOR-PROGNOSIS; SIRT1; EXPRESSION; CANCER; IDENTIFICATION; TRANSCRIPTION; COMPLEXITY; CANDIDATE; SPECTRUM;

D O I：

10.1016/j.celrep.2015.01.066

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

DBC1 (deleted in breast cancer 1), also known as CCAR2 or KIAA1967, is an important negative regulator of SIRT1 and cellular stress response. Although the Dbc1 gene localizes at a region that is homozygously deleted in breast cancer, its role in tumorigenesis remains unclear. It has been suggested to be either a tumor suppressor or an oncogene. Therefore, the function of DBC1 in cancer needs to be further explored. Here, we report that Dbc1 knockout mice are tumor prone, suggesting that DBC1 functions as a tumor suppressor in vivo. Our data suggest that the increased tumor incidence in Dbc1 knockout mice is independent of Sirt1. Instead, we found that DBC1 loss results in less p53 protein in vitro and in vivo. DBC1 directly binds p53 and stabilizes it through competition with MDM2. These studies reveal that DBC1 plays an important role in tumor suppression through p53 regulation.

引用

页码：1324 / 1334

页数：11

共 40 条

[1]

Analysis of DBC1 and its homologs suggests a potential mechanism for regulation of sirtuin domain deacetylases by NAD metabolites [J].