DBC1 functions as a tumor suppressor by regulating p53 stability

Bo Qin, Katherine Minter-Dykhouse, Jia Yu, Jun Zhang, Tongzheng Liu, Haoxing Zhang, Seung Baek Lee, Jung Jin Kim, Liewei Wang, Zhenkun Lou

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 invivo. 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 invitro and invivo. 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.

Original languageEnglish (US)
Pages (from-to)1324-1334
Number of pages11
JournalCell reports
Volume10
Issue number8
DOIs
StatePublished - Mar 3 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Qin, B., Minter-Dykhouse, K., Yu, J., Zhang, J., Liu, T., Zhang, H., Lee, S. B., Kim, J. J., Wang, L., & Lou, Z. (2015). DBC1 functions as a tumor suppressor by regulating p53 stability. Cell reports, 10(8), 1324-1334. https://doi.org/10.1016/j.celrep.2015.01.066