USP28

The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers.

ubiquitin specific peptidase 28

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).

Biological Process cell population proliferation Source:UniProtKB1 Publication
Biological Process cellular response to DNA damage stimulus Source:UniProtKB1 Publication
Biological Process cellular response to UV Source:UniProtKB1 Publication
Biological Process DNA damage checkpoint signaling Source:UniProtKB1 Publication
Biological Process DNA repair Source:UniProtKB-KW
Biological Process intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB3 Publications
Biological Process Ras protein signal transduction Source:UniProtKB1 Publication
Biological Process regulation of protein stability Source:UniProtKB1 Publication
Biological Process response to ionizing radiation Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Nucleus, nucleoplasm

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).