Proteins directly interacting with mammalian 20S proteasomal subunits and ubiquitin-independent proteasomal degradation.

Raúl Sánchez-Lanzas,José Castaño

doi:10.3390/biom4041140

Abstract

The mammalian 20S proteasome is a heterodimeric cylindrical complex (α7β7β7α7), composed of four rings each composed of seven different α or β subunits with broad proteolytic activity. We review the mammalian proteins shown to directly interact with specific 20S proteasomal subunits and those subjected to ubiquitin-independent proteasomal degradation (UIPD). The published reports of proteins that interact with specific proteasomal subunits, and others found on interactome databases and those that are degraded by a UIPD mechanism, overlap by only a few protein members. Therefore, systematic studies of the specificity of the interactions, the elucidation of the protein regions implicated in the interactions (that may or may not be followed by degradation) and competition experiments between proteins known to interact with the same proteasomal subunit, are needed. Those studies should provide a coherent picture of the molecular mechanisms governing the interactions of cellular proteins with proteasomal subunits, and their relevance to cell proteostasis and cell functioning.

Highlights

The proteasome is a 2.5 MDa complex formed by a proteolytic core particle (20S, CP), and is a cylindrical shaped complex with a heterodimeric structure (7777 subunits)
Proteins directly degraded by a ubiquitin-independent proteasomal degradation mechanism (UIPD) must belong to the large set of proteins that interact with the proteasome which include modulators or accessory proteins of proteasomal function
Proteasome subunits have been shown to interact with many cellular proteins; we have only described those, reported in specific published research papers, which interact with mammalian CP

Summary

Introduction

The proteasome is a 2.5 MDa complex formed by a proteolytic core particle (20S, CP), and is a cylindrical shaped complex with a heterodimeric structure (7777 subunits). Our aim is to provide a critical assessment of the research carried out in this area, by analyzing the specific interactions of mammalian cellular proteins with specific 20S (CP) proteasomal subunits This will enable identification of the set of proteins that interact with the proteasome, and a comparison of these proteins with the set of proteins degraded by the UIPD mechanism [2]. The PSMA4 subunit interacts with amino acids 40 to 60 of Hepatitis C virus F protein and promotes its UIPD [5]. The C-terminus of p21WAF1/CIP1 interacts with PSMA3 promoting its degradation by a UIPD mechanism [18] Apart from this direct interaction, several proteins have been shown to mediate presentation of p21 to the proteasome complex.

Ubiquitin Independent Proteasomal Degradation

Findings

Conclusions