Аннотация: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