HSPB6 (Hsp20) as a Versatile Molecular Regulator

Abstract

HspB6 (Hsp20) is a member of the large family of human small heat shock proteins. In contrast to other human small heat shock proteins (HspB1, HspB5) forming large oligomers, HspB6 predominantly forms stable dimers which tend to self-association. HspB6 is ubiquitously expressed in practically all human tissues, undergoes posttranslational modifi cations (such as phosphorylation and acetylation) and forms heterooligomeric complexes with two other human small heat shock proteins, HspB1 and HspB5. Possessing chaperone-like activity, HspB6 prevents aggregation of amyloid-β and α-synuclein, decreases cytotoxicity induced by accumulation of amyloids and, interacting with Bag3, modulates autophagosomal degradation of misfolded proteins. HspB6 protects cardiomyocytes from ischemia/reperfusion injuries, prevents cardiac hypertrophy and, possessing antiapoptotic activity, protects cardiomyocytes from different unfavorable conditions. Phosphorylation of HspB6 catalyzed by cyclic nucleotide-dependent protein kinases induces relaxation of different smooth muscle. Exact molecular mechanism underlying relaxation effect of phosphorylated HspB6 in smooth muscle remains enigmatic, but seems to be dependent on the remodeling of actin cytoskeleton. HspB6 is not a genuine actin-binding protein, but interacting with universal adapter protein 14-3-3 seems to be able indirectly affect activity of certain regulatory actin-binding proteins thus inducing cytoskeleton remodeling. Penetrating phosphorylated peptides of HspB6 were successfully used for relaxation of airway smooth muscle and prevention of vasospasm in human blood vessels. Full-size HspB6 and its short peptides modulate platelet aggregation. Versatility of HspB6 is awaiting further investigation, however it can be at least partially explained by the ability of phosphorylated HspB6 to interact with the universal adapter protein 14-3-3 and to displace different target proteins from their complexes with 14-3-3. This displacement may result in modulation of target protein activity and consequently can induce multiple and diverse effects.

The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90

“…The primary structure of Hsp27 is highly homologous to other members of the sHsp family that bear the conserved α-crystallin domain (ACD) and variable-length N- and C-terminal regions (NTRs and CTRs, respectively) [ 34 ]. Hsp27 is an ATP-dependent chaperone that folds substrate proteins and participates in shuttling destabilized or misfolded proteins toward proteolytic degradations [ 35 ]. Hsp27 is cytoprotective; it blocks apoptosis through interaction with various factors active in the apoptotic pathway [ 36 ].…”