ubiquitin carboxyl-terminal hydrolase 28; deubiquitinating enzyme 28; ubiquitin thiolesterase 28; ubiquitin-specific-processing protease 28 (USP28, KIAA1515)
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Function
- deubiquitinase involved in DNA damage response checkpoint & MYC proto-oncogene stability
- involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway including CLSPN
- role in G2 DNA damage checkpoint, by deubiquitinating CLSPN, & 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 preventing MYC degradation by the proteasome
- specifically interacts with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm & counteracts 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 & explaining the selective MYC degradation in the nucleolus
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
- degradaded upon nickel ion level or hypoxia exposure
- phosphorylated upon DNA damage at Ser-67 & Ser-714, by ATM or ATR
- interacts with isoform 1 of FBXW7;
- following DNA damage, dissociates from FBXW7 leading to degradation of MYC
Structure
- belongs to the peptidase C19 family, USP28 subfamily
- contains 1 UIM (ubiquitin-interacting motif) repeat
Compartment
Alternative splicing
named isoforms=2
Expression
down-regulated upon hypoxia