The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc
Abstract
c-Myc is ubiquitinated by SCF Fbw7 and appears to be degraded mainly in the nucleolus, where it acts as a master regulator of ribosomal biogenesis. However, deubiquitination regulation of c-Myc in the nucleolus is previously unknown. Here, we found that ubiquitin-specific protease 36 (USP36), a nucleolar ubiquitin-specific protease, interacts with and deubiquitinates c-Myc in the nucleolus. It also interacts with Fbw7γ but not Fbw7α, yet it abolishes c-Myc degradation mediated by either Fbw7γ or Fbw7α. Ablation of USP36 reduced c-Myc levels and severely inhibited cancer cell proliferation. USP36 is overexpressed in a subset of human breast and lung cancers. Thus, our study reveals USP36 as a novel deubiquitinating enzyme controlling c-Myc’s nucleolar degradation, adding a missing and end-point regulator into the c-Myc degradation pathway.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 09, 2015
- Source ID
- 10.1073/pnas.1411713112
Entities
People
- Li Yin
- Masayuki Komada
- Mu-Shui Dai
- Rosalie C Sears
- Xia He
- Xiao-xin Sun
Organizations
- Congressionally Directed Medical Research Programs
- Jiangsu Cancer Hospital
- National Cancer Institute
- Tokyo Institute of Technology