Deubiquitinating Enzyme USP29 Regulates the Protein Stability of CBX6 / 中国生物化学与分子生物学报

ABSTRACT

Polycomb group (PcG) proteins are transcriptional repressors that control cell fate and the development of embryo, and they elicit function mainly in the form of polycomb repressive complex (PRC). Chromobox protein homolog 6 (CBX6) is one of the core protein subunits of PRC1, which plays an important role in gene expression regulation, cell renewal and differentiation, tumorigenesis and development, and stem cell maintenance. In this study, CBX6 was found to be degraded through a ubiquitin-proteasome dependent pathway. Then the gene expression library containing 92 deubiquitinating enzymes (DUB) was used to screen DUB targeting CBX6 and results found that ubiquitin-specific protease 29 (USP29) could obviously stabilize CBX6 protein level and extend its half-life (P < 0.05). Immunoprecipitation experiments found that CBX6 interacted with USP29 through its C-terminal domains; Further studies found that USP29 regulated the protein stability of CBX6 by deubiquitination in an enzymatic-activity dependent manner. Cell proliferation assay also found that USP29 inhibited the proliferation of MCF7 cells (P<0.0001). Taken together, through screening, this study found that USP29 could stabilize CBX6 protein level through deubiquitinating CBX6 and inhibit the cell proliferation of MCF7.