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Biomedical Research Journal

Volume 3, Issue 1, April 2016, Pages 23-51

Review

Assembly and Beyond – The Structure and Functions of Chaperones of the Proteasome

Prasanna Venkatraman*

Advanced Centre for Training, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai – 410210, India.

The 26S proteasome is the major protease machinery in eukaryotic cells responsible for spatio-temporally regulated turnover of the proteome and therefore critical to the maintenance of homeostasis. These act not only as efficient garbage disposal units for abnormal/misfolded, denatured and oxidised proteins, but, are crucial for irreversible termination of key cellular process regulation of various check points. Replication, transcription, translation, antigen processing, maintenance of stemness, development and differentiation are several of the functions and processes regulated by the proteasomes. The 2.5-megadalton structure of the eukaryotic proteasome is very complex and is assembled from 66 polypeptides with 33 structurally unique. The biogenesis of the multi subunit architecture is regulated by dedicated chaperones which orchestrate the assembly of intricate and complex structure. The current review focuses on four chaperones PSMD9 (Nas2), PSMD10 (Nas6), PAAF1 (Rpn14) and S5B (Hsm3) responsible for the assembly. The structure of the chaperones, molecular details of interaction of the individual chaperones with subunits of the proteasome during the process of assembly, role in hierarchical steps leading to assembly, recent evidences for the unprecedented role of some of these proteins (PSMD9 and PSMD10) in other physiological processes will be summarized. In addition, potential of two chaperones as targets for development of inhibitors of proteasome function will be explored.

Keywords:

Proteasome, chaperone, PSMD9, gankyrin, interaction, NF-kB

*Corresponding Author:

Prasanna Venkatraman, Protein Interactome Lab for Structural and Functional Biology, Advanced Centre for Training Reasearch and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai – 410210, India. E mail: vprasanna@actrec.gov.in; Tel: +91-22-27405091; Fax: +91-022-27405085

Cite this article as:

Venkatraman P. Assembly and Beyond – The structure and functions of chaperones of the proteasome. Biomed Res J 2016;3(1):23-51.

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