Small heat shock proteins: a new classification scheme in mammals.
Small MW heat shock proteins (i.e. sHSPs approximately 15-30 kDa) share significant sequence similarity within the "alpha-crystallin domain" but exhibit different patterns of gene expression, transcriptional regulation, sub-cellular localization, and, perhaps, function. The chaperone-like properties of many sHSPs are defined biochemically by their ability to prevent protein aggregation and/or restore biological activity of client substrates in vitro. Furthermore, such functions are widely believed to mitigate protein misfolding and denaturation triggered by noxious environmental stimuli such as hyperthermia stress, decreased pH(i), osmotic stress, heavy metals, hypoxia, and ischemic injury in vivo. At least 10 mammalian sHSPs, several with tissue-restricted expression, have been identified in recent genome surveys of mice, rats, and humans, but their functions have remained poorly understood. Here, we propose a simple classification scheme for sHSPs to reflect emerging evidence that their specialized roles (e.g. apoptosis, protein trafficking, redox control, and cytoskeletal interactions) might be inextricable linked to both coordinate regulation and multimeric protein complexes in a lineage-specific manner. Thus, Class I proteins display ubiquitous expression, whereas the tissue distribution of Class II proteins is primarily restricted to myogenic and testicular lineages. Because the expression patterns and modifications of sHSPs are potentially surrogate biosignatures for underlying pathophysiological events, we propose that this classification should accelerate progress to define the functional diversification for sHSPs especially in selective tissues predisposed to inheritable, degenerative, and other acquired diseases in humans.
Taylor
Ryan P
RP
The University of Utah Health Sciences Center, Division of Cardiology, Salt Lake City, UT 84112, USA.
Benjamin
Ivor J
IJ
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D010802:Phylogeny; D051381:Rats; D017386:Sequence Homology, Amino Acid
D006360:Heat-Shock Proteins