HSP26 and HSP42 encode the cytosolic members of the small heat shock protein (sHSP) family of molecular chaperones (6, 2). sHSPs bind and prevent unfolded substrate proteins from irreversibly forming large protein aggregates. Bound substrate proteins can eventually be released and refolded in either a spontaneous or chaperone-assisted manner (reviewed in 7). Hsp42p functions in both unstressed and stressed cells, while Hsp26p activity is found only under stress conditions; the target substrate profiles of the two chaperones overlap by approximately 90% (4). Null mutations in hsp26 or hsp42 cause abnormal cell morphology that resembles the effects of dehydration, aging, cytoskeleton damage, or cell wall damage (4).

A basal level of the HSP42 transcript is found under all conditions but expression is induced by stresses such as heat shock, salt shock, and starvation (2). This upregulation of transcription is mediated by the transcription factors Hsf1p and Msn2p/Msn4p which respectively bind heat shock elements and stress elements found in the HSP42 promoter (8, 9). Like other sHSPs, Hsp42p forms a large homo-oligomeric complex; the Hsp42p complex is a ring/barrel-like structure comprised of homodimers (4).

All sHSP chaperones contain a highly conserved alpha-crystallin domain in their C-terminus, and sHSPs have been identified in archaea, plants, insects, cows, and humans (10, 11). Mutations in human sHSPs have been linked to the cardiovascular disorder desmin-related myopathy (OMIM), the neuromuscular disease Charcot-Marie-Tooth disease (OMIM), distal hereditary motor neuropathy (OMIM), and hereditary cataracts (OMIM) (12 and references therein).

Last updated: 2007-07-26