USP28
USP28 (ubiquitin specific peptidase 28, also known as KIAA1515) is a nucleoplasmic deubiquitinase that removes ubiquitin from substrates in the DNA damage response and from the transcription factor MYC. It belongs to the peptidase C19 family, USP28 subfamily. Browse Assay Genie's current range of USP28 research reagents below, or read on for the biology behind the target.
USP28 is a deubiquitinase that acts in the DNA damage response checkpoint and in control of MYC proto-oncogene stability. By removing ubiquitin from specific substrates, it protects them from proteasomal or APC/C-mediated degradation. In DNA damage-induced apoptosis it deubiquitinates proteins of the DNA damage pathway such as CLSPN. It also contributes to the G2 DNA damage checkpoint by deubiquitinating CLSPN and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). It does not deubiquitinate PLK1, which illustrates the selectivity of the enzyme.
In the nucleoplasm, USP28 deubiquitinates MYC and so prevents its degradation by the proteasome. It does this by interacting specifically with isoform 1 of FBXW7 (FBW7alpha) and counteracting MYC ubiquitination by the SCF(FBW7) complex. It does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, which allows MYC degradation there and explains the selective MYC degradation in that compartment. USP28 also deubiquitinates ZNF304, preventing its proteasomal degradation. This leads to KRAS-mediated promoter hypermethylation and transcriptional silencing of tumour suppressor genes in a subset of colorectal cancer cells.
The USP28 gene is a member of the HGNC ubiquitin specific peptidases group, and the enzyme is catalogued as EC 3.4.19.12. Its previous name was ubiquitin specific protease 28, and KIAA1515 is a legacy alias. Overexpression of the gene is seen in several cancers, which makes the USP28 protein a frequent subject in studies of ubiquitin signalling and tumour biology. Orthologous Usp28 genes are annotated in mouse and rat.
USP28 deubiquitinates CLSPN and supports the G2 DNA damage checkpoint and DNA damage-induced apoptosis.
USP28 counteracts SCF(FBW7)-mediated ubiquitination of MYC in the nucleoplasm, preventing its proteasomal degradation.
Through ZNF304 stabilisation, USP28 is linked to KRAS-driven silencing of tumour suppressor genes in a subset of colorectal cancer cells.
As a peptidase C19 family deubiquitinase, USP28 is a model for substrate-selective control of protein turnover.
USP28 is a deubiquitinase that removes ubiquitin from selected substrates. It supports the DNA damage checkpoint by stabilising CLSPN, prevents proteasomal degradation of MYC in the nucleoplasm, and stabilises ZNF304, which is relevant to gene silencing in some colorectal cancer cells.
The HGNC name is ubiquitin specific peptidase 28, and UniProt lists ubiquitin carboxyl-terminal hydrolase 28. The previous name was ubiquitin specific protease 28, and KIAA1515 is a recorded alias. The enzyme is classified as EC 3.4.19.12 and belongs to the USP28 subfamily of peptidase C19.
NCBI Gene reports overexpression of USP28 in several cancers, and its roles in MYC stability and tumour suppressor gene silencing fit this link. Mouse and rat both have a Usp28 ortholog; check the datasheet of any product for its validated reactivity.
Other ubiquitin specific peptidases and deubiquitinases involved in protein turnover and DNA damage signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q96RU2; product specifications from Assay Genie datasheets.