USP28

Description

The USP28 (ubiquitin specific peptidase 28) is a protein-coding gene located on chromosome 11.

USP28 is a deubiquitinase that plays a role in the DNA damage response checkpoint and MYC proto-oncogene stability. It is involved in DNA damage-induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway, such as CLSPN. USP28 also participates in the G2 DNA damage checkpoint by deubiquitinating CLSPN and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). However, it does not deubiquitinate PLK1. USP28 specifically deubiquitinates MYC in the nucleoplasm, preventing MYC degradation by the proteasome. It interacts with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracts ubiquitination of MYC by the SCF(FBW7) complex. In contrast, USP28 does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. USP28 deubiquitinates ZNF304, preventing its degradation by the proteasome. This leads to activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancer (CRC) cells. USP28 interacts with ZNF304, PRKD1, TP53BP1, and isoform 1 of FBXW7. Following DNA damage, USP28 dissociates from FBXW7 leading to degradation of MYC.

USP28 is also known as -.

Associated Diseases

WES Whole Exome Sequencing