Proteasomal complex regulation by heat‐shock proteins in cancer

Abstract

Proteasome mediated protein degradation is a major component of the cellular machinery that maintains the protein homeostasis. The disruption of the proteasomal function induces proteotoxic stress and activates the cellular heat shock response. There are two distinct proteasomal degradation pathways, the ubiquitin dependent proteasome pathway mediated by the 26S proteasomes and the ‐ubiquitin independent proteasomal degradation pathway mediated by the 20S proteasome. The cross talk between the chaperone and ubiquitin system has been highly explored and characterized, however little is known on the direct regulation of heat shock proteins on proteasomal integrity and function in mammalian cells. In this work we try to set the framework to examine the regulatory roles that Hsps might have in regulating proteasomal complex function and integrity. By using high throughput protein‐protein interaction assays and masspectrometry we examine the association of cellular proteins specifically chaperones to the proteasomal machinery following proteotoxic stresses. Our work examines the regulatory role of Hsps in maintaining protein homeostasis by directly regulating the proteasomal complex function and how this interplay contributes to cancer cell proliferation.