HSP27

Hsp27, also known as HSPB1, is a member of the small heat shock protein (sHSP) family. It functions primarily as a molecular chaperone that helps maintain protein homeostasis, especially under stress, by preventing the aggregation of unfolded proteins and facilitating their refolding in cooperation with the Hsp70 chaperone system.

Structure and regulation: Hsp27 forms large oligomers in the cytosol that can dissociate into smaller units. Phosphorylation at serine residues 15, 78, and 82 regulates oligomerization and chaperone activity. Kinases such as MAPKAP kinase-2 (MK2) and other stress-activated kinases mediate these modifications in response to cellular stress.

Functions: In addition to proteostasis, Hsp27 stabilizes cytoskeletal elements including actin filaments and intermediate filaments, helping to preserve cell architecture during stress. It can interact with apoptotic signaling proteins, sequester cytochrome c, and inhibit caspase activation, contributing to cell survival.

Clinical relevance: Hsp27 is overexpressed in several cancer types and is associated with resistance to chemotherapy and poor prognosis in some contexts, making it a target for therapy. Antisense oligonucleotides such as apatorsen (OGX-427) have been investigated to reduce HSP27 levels in tumors. Beyond cancer, Hsp27 is studied for potential protective roles in neurodegenerative diseases and cardiac ischemia, although its effects are context-dependent.

Localization and expression: Predominantly cytosolic, with occasional nuclear localization. Expressed broadly in many tissues, with notably high levels in muscle and nervous tissue.