A comparison of Hsp90α and Hsp90β interactions with cochaperones and substrates

Abstract

Hsp90 chaperone complexes function in assembly, folding, and activation of numerous substrates. The 2 vertebrate homologues encoded by the genes hsp90a and hsp90b are differentially expressed in embryonic and adult tissues and during stress; however, it is not known whether they possess identical functional activities in chaperone complexes. This question was addressed by examining potential differences between the Hsp90 isoforms with respect to both cochaperone and substrate interactions. Epitope-tagged proteins were expressed in mammalian cells or Xenopus oocytes and subjected to immunoprecipitation with an array of co-chaperones. Both isoforms were shown to participate equally in multichaperone complexes, and no significant differences in cochaperone distribution were observed. The substrates Raf-1, HSF1, Cdc37, and MEK1 interacted with both Hsp90alpha and Hsp90beta, and the relative patterns of these interactions were not affected by heat shock. The substrate kinases c-Src, CKIIB, A-raf, and Erk interacted with both isoforms; however, significantly more Hsp90alpha was recovered after heat shock. The data demonstrate that Hsp90alpha and Hsp90beta exhibit similar interactions with co-chaperones, but significantly different behaviors with respect to substrate interactions under stress conditions. These results reveal both functional similarities and key functional differences in the individual members of this protein family.

Regulation and function of the human HSP90AA1 gene

“…Work done in Xenopus eggs and yeast has shown that Hsp90α and Hsp90β differ in co-chaperone and client interactions (Taherian et al 2008; Gong et al 2009). However, little is understood concerning the unique functions delegated to each paralog.…”

“…Each of these domains contain post-translational modification (PTM) sites. Within the Hsp90α protein, sequence specific post-translational modification sites are found (Taherian et al 2008; Quanz et al 2012; Muller et al 2013). This allows for further regulation of Hsp90α-specific cellular functions.…”

Chaperoning steroidal physiology: Lessons from mouse genetic models of Hsp90 and its cochaperones

“…Although Hsp90β is constitutively expressed, Hsp90α expression is highly-inducible by heat shock and other forms of stress [23]. Most in vitro studies show that each isoform displays the same preferences for cochaperones and clients, with the exception that some client substrates, such as c-Src and A-raf, preferentially bind Hsp90α following heat shock [25]. However, some cellular processes appear to specifically require Hsp90α, such as caspase-2 activation [26], maturation of metalloprotease 2 in the extracellular matrix and invasiveness of some metastatic cancers [27].…”

Toxicology mechanism of the persistent organic pollutants (POPs) in fish through AhR pathway

“…As far as the zebrafish is concerned Hsp90α gene is strongly expressed following heat shock, whereas the Hsp90β is only weakly up-regulated under similar stress conditions (Krone and Sass 1994). These results reveal both functional similarities and key functional differences in the individual members of this protein family (Taherian et al 2008).…”