FEATURES

FAMILY

DESCRIPTION

Also known as UBP28_HUMAN, USP28, KIAA1515. Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306). Interacts with ZNF304 (PubMed:24623306). Interacts with PRKD1 (PubMed:24623306). Interacts with TP53BP1 (PubMed:16901786). Interacts with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC (PubMed:17873522, PubMed:17558397).

EXTERNAL LINKS

USP28

Mutations

Mutation(s) distribution

Mutations table