Function and mechanism of PA200 proteasome-mediated protein degradation

Abstract

<p indent="0mm">Proteasomes are responsible for the timely, efficient, and irreversible degradation of most cellular proteins and are critical to almost all cellular activities. Proteasomes are important drug targets. Several proteasome inhibitors are being used to treat multiple myeloma and mantle cell lymphoma. Three forms of proteasomes have been described: the typical 26S proteasome, the PA28 proteasome, and the PA200 proteasome. The 26S proteasome, which degrades ubiquitinated substrates, is the major type of proteasome. The PA28 proteasome is an immunoproteasome that plays a critical role in antigen presentation. The PA200 proteasome degrades core histones in an acetylation-dependent manner. The post-translational modification mode of core histones is known as “epigenetic codes,” thus, guiding the epigenetic regulation of gene expression. The PA200-containing proteasome in testes is specialized into a spermatoproteasome, with the α4s testis-specific subunit. This review summarizes the distribution, structure, and assembly mechanisms of the PA200 proteasome and outlines its functions in histone degradation, DNA repair, spermatogenesis, aging, and epigenetic regulation. This study will facilitate an understanding of the molecular mechanisms of reproduction, development, and aging and provide a basis for diagnosis and treatment of related diseases, such as male infertility, Alzheimer’s disease, and cancer.