USP28 Mouse Monoclonal Antibody [A1F8]

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.

Background References

1. Serra R.W. et. al. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife 3:E02313-E02313(2014).

2. Bassermann F. et. al. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 134:256-267(2008).

Sequence Similarity

Belongs to the peptidase C19 family. USP28 subfamily.

Post-translational Modification

Degraded upon nickel ion level or hypoxia exposure.; Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR. Phosphorylated by PRKD1.

Subcellular Location

Nucleoplasm.

UNIPROT

SwissProt: Q96RU2 Human

Synonyms