title: Deubiquitinating c-Myc: USP36 steps up in the nucleolus.
abstract: Ubiquitination plays a key and complex role in the regulation of c-Myc stability, transactivation, and oncogenic activity. c-Myc is ubiquitinated by a number of ubiquitin ligases (E3s), such as SCF(Fbw7) and SCF(Skp2). Depending on the E3s, ubiquitination can either positively or negatively regulate c-Myc levels and activity. Meanwhile, c-Myc ubiquitination can be reversed by deubiquitination. An early study showed that USP28 deubiquitinates c-Myc via interacting with Fbw7α whereas a recent study reveals that USP37 deubiquitinates c-Myc independently of Fbw7 and c-Myc phosphorylation. Consequently, both USP28 and USP37 stabilize c-Myc and enhance its activity. We recently found the nucleolar USP36 as a novel c-Myc deubiquitinase that controls the end-point of c-Myc degradation pathway in the nucleolus. Here we briefly review the current understanding of ubiquitination and deubiquitination regulation of c-Myc and further discuss the USP36-c-Myc regulatory pathway.
authors.affiliation: a Departments of Molecular & Medical Genetics ; School of Medicine and the OHSU Knight Cancer Institute; Oregon Health & Science University ; Portland , OR USA.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Sun
authors.affiliation: a Departments of Molecular & Medical Genetics ; School of Medicine and the OHSU Knight Cancer Institute; Oregon Health & Science University ; Portland , OR USA.
authors.forename: Rosalie C
authors.initials: RC
authors.lastname: Sears
authors.affiliation: a Departments of Molecular & Medical Genetics ; School of Medicine and the OHSU Knight Cancer Institute; Oregon Health & Science University ; Portland , OR USA.
authors.forename: Mu-Shui
authors.initials: MS
authors.lastname: Dai
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: D016271:Proto-Oncogene Proteins c-myc; C442902:USP28 protein, human; C501066:USP36 protein, human; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; C559980:USP37 protein, human
keywords: USP36; c-Myc; deubiquitinating enzymes; nucleolus; ubiquitination