USP28
Function
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).
Post-translational modifications
Degraded upon nickel ion level or hypoxia exposure.
Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR (PubMed:16901786). Phosphorylated by PRKD1 (PubMed:24623306).
Sequence Similarities
Belongs to the peptidase C19 family. USP28 subfamily.
Cellular localization
- Nucleus
- Nucleoplasm
Alternative names
KIAA1515, USP28, Ubiquitin carboxyl-terminal hydrolase 28, Deubiquitinating enzyme 28, Ubiquitin thioesterase 28, Ubiquitin-specific-processing protease 28