Molecular Function Of USP27x And The Association With Tumorgenesis

Deubiquitination enzymes specifically hydrolyse off the ubiquitin from the target protein or the precursor protein by hydrolysing the carboxyl-terminal peptide bond, peptide bond or isobutyl ester bond of ubiquitin, which can protect the target protein from the degradation through the ubiquitin-proteasome pathway. USP27x(Ubiquitin Carboxyl-terminal Hydrolase 27) is a member of the USP family, whose ORF is 1317 bp and encodes 438 amino acids, with a predicted USP active catalytic domain. USP27x has 82% homology with USP22 of the same USP family by bioimformatics analysis. With little report about USP27x, the biochemical characteristics and biological function of USP27x are still unclear now.Our research found that USP27x protein is widely expressed in human tissues, with its highest expression in liver and pancreas and low expression in lungs and mammary gland..Immunohistochemical and immunofluorescence results shown that USP27x is mainly localized in the cytoplasm while USP22 is localized in the nucleus.Based on this obvious difference,we hypothesized that their biological functions may be different..In order to determine whether USP27x has ability to regulate other proteins, we firstly veritied its activity as a deubiquitination enzyme in vitro, then screened for the change of protein molecule in cells by overexpressing USP27x. We found that increased USP27x can lead to the increased amount of p21 protein expression, while this increase is disappeared after using MG132, suggesting that the way of USP27x regulating p21 protein level is in proteasome pathway.The control ability of USP27x to p21 makes us speculate USP27x probably mediated the malignant biological behavior of tumor cells. So by cloning forming experiment and MTT experiment we found that the expression of USP27x can promotes the proliferation of breast cells MCF-7.The the cell cycle experiment showed that overexpressed USP27x causes a decline in the cell cycle G1 phase as well as an increase in S phase, and promotes cell cycle G1 phase to S phase transformation.This study preliminary revealed the biochemical characteristics molecular function in cells and the relationship to the tumor of USP27x, which laid a foundation for further in-depth study on the function of USP27x in cell and for revealing the molecular mechanism on how it mediated tumor proliferation.