Hsp70B′ regulation and function

Abstract

Heat shock protein (Hsp) 70BЈ is a human Hsp70 chaperone that is strictly inducible, having little or no basal expression levels in most cells. Using siRNAs to knockdown Hsp70BЈ and Hsp72 in HT-29, SW-480, and CRL-1807 human colon cell lines, we have found that the two are regulated coordinately in response to stress. We also have found that proteasome inhibition is a potent activator of hsp70BЈ. Flow cytometry was used to assay hsp70BЈ promoter activity in HT-29eGFP cells in this study. Knockdown of both Hsp70BЈ and Hsp72 sensitized cells to heat stress and increasing concentrations of proteasome inhibitor. These data support the conclusion that Hsp72 is the primary Hsp70 family responder to increasing levels of proteotoxic stress, and Hsp70BЈ is a secondary responder. Interestingly ZnSO 4 induces Hsp70BЈ and not Hsp72 in CRL-1807 cells, suggesting a stressor-specific primary role for Hsp70BЈ. Both Hsp70BЈ and Hsp72 are important for maintaining viability under conditions that increase the accumulation of damaged proteins in HT-29 cells. These findings are likely to be important in pathological conditions in which Hsp70BЈ contributes to cell survival.

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

“…2A-C). Such factors are critical for adaptive responses to stress and thus cell survival (33). Several of these RHOX-regulated genes have been shown to have crucial roles in human male reproduction.…”

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

“…expression [29]. HSPA6 is closely related to HSP72 sharing 93% protein sequence homology and may have an overlapping function [17].…”

Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

“…This includes upregulation of HSPA6 (Hsp70B'), a little studied member of the HSPA (Hsp70) family that is present in the human genome, but not in rat and mouse (Chow and Brown 2007;Noonan et al 2007aNoonan et al , b, 2008aChow et al 2010;Ramirez et al 2014). Recently, we have demonstrated a unique feature of HSPA6, namely localization to transcription sites in human neuronal cells during recovery from stress-induced inhibition (Khalouei et al 2014), a feature that is missing in current animal models of neurodegenerative diseases which lack HSPA6.…”