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.
Western blot analysis of USP28 on different lysates with Mouse anti-USP28 antibody (EM1901-46) at 1/2,000 dilution.
Lane 1: HeLa cell lysate Lane 2: A431 cell lysate Lane 3: 293T cell lysate Lane 4: SW480 cell lysate Lane 5: LNCaP cell lysate Lane 6: MDA-MB-231 cell lysate Lane 7: MDA-MB-468 cell lysate Lane 8: Rat testis tissue lysate
Lysates/proteins at 20 µg/Lane.
Predicted band size: 122 kDa Observed band size: 140 kDa
Exposure time: 3 minutes;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (EM1901-46) at 1/2,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Mouse IgG - HRP Secondary Antibody (HA1006) at 1/50,000 dilution was used for 1 hour at room temperature.
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