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

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 FBW7alpha, 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 FBW7gamma. High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation.

Top
  1. Institute of Molecular Biology and Tumor Research, Emil-Mannkopff-Str.2, 35033 Marburg, Germany.
  2. Netherlands Cancer Institute, Division of Molecular Carcinogenesis, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
  3. Department of Genetics, Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  4. Department of Pathology, University of Marburg, Baldingerstrasse, 35033 Marburg, Germany.

Correspondence to: Martin Eilers1 e-mail: eilers@imt.uni-marburg.de



Extra navigation

Subscribe to Nature Cell Biology

Subscribe

See also

Search PubMed for

natureproducts