Proteomics of proteasome complexes and ubiquitinated proteins

Abstract

Ubiquitin–proteasome-mediated protein degradation is central to the regulation of many important biological processes, including cell cycle progression, apoptosis and DNA repair. Recognition and degradation of ubiquitinated substrates by the 26S proteasome is tightly regulated to maintain normal cell growth. Disruption of the proteasomal degradation pathway has been implicated in a wide range of human diseases. Although the ubiquitin–proteasome system has been intensively investigated, many key questions remain unanswered in regard to its components and regulation of its activities. A key step towards a full understanding of the pathway is to investigate the proteasome complex subunit composition, heterogeneity, post-translational modifications, assembly, proteasome interaction networks and degradation substrates. Mass spectrometry-based proteomic approaches have been successfully applied for unraveling the details of the proteasome complexes and their substrates in an unprecedented fashion. An overview of the current knowledge of the proteasomal degradation pathway based on mass spectrometry approaches is presented.

Keywords::

• proteasome complex
• mass spectrometry
• protein degradation
• protein post-translational modification
• protein–protein interaction
• proteomics
• QTAX
• ubiquitination
• ubiquitin chain topology

Financial & competing interests disclosure

This work was supported by National Institutes of Health grants (GM74830 to Lan Huang and GM-66164 to Peter Kaiser), the Deptartment of the Army (PC-041126 to Lan Huang), the California Breast Cancer Research Program (11NB-0177 to Peter Kaiser).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.