Article abstract
Nature Cell Biology 9, 765 - 774 (2007)
Published online: 10 June 2007 | doi:10.1038/ncb1601
The ubiquitin-specific protease USP28 is required for MYC stability
Nikita Popov1, Michael Wanzel1, Mandy Madiredjo2, Dong Zhang3, Roderick Beijersbergen2, Rene Bernards2, Roland Moll4, Stephen J. Elledge3 & Martin Eilers1
Abstract
The MYC proto-oncogene encodes a transcription factor that has been implicated in the genesis of many human tumours. Here, we used a bar-code short hairpin RNA (shRNA) screen to identify multiple genes that are required for MYC function. One of these genes encodes USP28, an ubiquitin-specific protease. USP28 is required for MYC stability in human tumour cells. USP28 binds to MYC through an interaction with FBW7
, an F-box protein that is part of an SCF-type ubiquitin ligase. Therefore, it stabilizes MYC in the nucleus, but not in the nucleolus, where MYC is degraded by FBW7
. High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation.
- Institute of Molecular Biology and Tumor Research, Emil-Mannkopff-Str.2, 35033 Marburg, Germany.
- Netherlands Cancer Institute, Division of Molecular Carcinogenesis, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
- Department of Genetics, Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
- Department of Pathology, University of Marburg, Baldingerstrasse, 35033 Marburg, Germany.
Correspondence to: Martin Eilers1 e-mail: eilers@imt.uni-marburg.de
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