From: Therapeutic potential of Hsp27 in neurological diseases
Phosphorylation sites | Stress inducibility | Metal ion interaction | α-Synuclein formation | Amyloid aggregation and cytotoxicity | Metal ion-induced aggregation of amyloid and α-synuclein and oxidative stress | Functions | |
---|---|---|---|---|---|---|---|
Hsp27 (HSPB1) | Human—MK2-, MK3-, and MK5-mediated phosphorylation at S15, S78, and S82 residues. Chinese hamster—S15, S90 residues. Murine Hsp25 (HSPB1)—phosphorylation by protein kinase C and cAMP-dependent kinase at S15 and S86 residues. | Positive | Expression is induced by Cu2+and also by Cd2+. | Prevent | Inhibit aggregation but does not have a role in preventing cytotoxicity | Protective role in Cu2+- induced aggregation and oxidative stress | Modulates p53 pathway by inhibiting cellular senescence and also prevents apoptosis by interfering both caspase-dependent and caspase-independent pathways. It also possesses chaperone activity and also prevents the cell death pathway triggered by a rise in levels of ROS. |
Hsp20 (HSPB6) | Protein kinase A (PKA)/protein kinase G (PKG) phosphorylation at S16 residue. | Negative | – | Prevent | Prevent aggregation and attenuate cytotoxicity | – | Phosphorylation at S16 residue leads to antiapoptotic function where it inhibits mitochondria-mediated apoptosis [30]. It also possesses chaperone activity. |
α-Crystallin | α-A crystallin (HSPB4)—cAMP-dependent kinase-mediated phosphorylation at S122 and 3 other phosphorylation sites between 122 and 178 residues. α-B crystallin (HSPB5)—phosphorylation at S19 residue which is age-dependent, S45 residue during mitosis and in heat stress conditions at S59 residue. | α-A crystallin—negative α-B crystallin—positive | α-A crystallin expression is induced by Cu2+ and Zn2+. α-B crystallin expression is induced by Cu2+ and also by Cd2+ and Zn2+. | Prevent | Inhibit aggregation and prevent cytotoxicity | Protective role in Cu2+-induced aggregation and oxidative stress | Prevent TNFα-mediated apoptosis, mitochondria-mediated apoptosis, and cytochrome c interaction in apoptosis. It also modulates P53 pathway involving senescence and chaperone activity. |
Hsp22 (HSPB8) | cAMP-dependent protein kinase phosphorylation at S24 and S57 residues. | Positive based on cell type | – | Prevent and are more potent in nature | Inhibit aggregation and cytotoxicity | – | Major function is chaperone activity. It is actively involved in macroautophagy. |