The ubiquitin-specific protease USP28 is required for MYC stability.
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.
Popov
Nikita
N
Institute of Molecular Biology and Tumor Research, Emil-Mannkopff-Str.2, 35033 Marburg, Germany.
Wanzel
Michael
M
Madiredjo
Mandy
M
Zhang
Dong
D
Beijersbergen
Roderick
R
Bernards
Rene
R
Moll
Roland
R
Elledge
Stephen J
SJ
Eilers
Martin
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D044783:F-Box Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000502:physiology*
D044783:F-Box Proteins; C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; C442902:USP28 protein, human; D044843:SKP Cullin F-Box Protein Ligases; D043222:Ubiquitin Thiolesterase