HSPB1 gene

The HSPB1 gene (HSPB1 stands for: Heat Shock Protein Family B (Small) Member 1) is a protein-coding gene located on chromosome 7q11.23.

The HSPB1 gene encodes a member of the family of small heat shock proteins (HSP20). In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and acts as a molecular chaperone that promotes the correct folding of other proteins. The encoded small heat shock protein plays an important role in the differentiation of a variety of cell types, including keratinocytes (Scieglinska D et al. 2019).

The expression of this gene correlates with negative clinical outcomes in various human cancers. It promotes the proliferation and metastasis of cancer cells, but at the same time protects cancer cells from apoptosis.

The encoded HSP20 protein probably maintains denatured proteins in a folding-competent state. It also plays a role in stress resistance and actin organization. Can regulate numerous biological processes through its molecular chaperone activity, including phosphorylation and axonal transport of neurofilament proteins (Rogalla T et al.1999)

The HSPB family comprises several members, some of which are ubiquitously expressed and others expressed in a cell type-specific manner. Of several members of the human HSPB family, only HSPB1 has been studied in the context of keratinocyte biology. HSPB1 is a stress-inducible chaperone that is involved in transferring unfolded peptides to the HSPA-HSPC-HSPH chaperone machinery with its so-called holdase activity, helping them to reach their native structure and prevent non-specific aggregation (reviewed in: Hilton et al. 2013; Treweek et al. 2014). Structural modifications of HSPB1, which include oligomerization and specific phosphorylation patterns, are thought to be crucial for regulating its interaction with specific clients and shaping its cell type- and state-specific functions (Arrigo 2013). Under cellular stress, part of the HSPB1 protein pool migrates from the cytoplasm to the nucleus (Bryantsev et al. 2007) and/or can be secreted outside the cell (Pockley et al. 2014). HSPB1, which is considered one of the most important elements of cellular proteostasis, is functionally involved in numerous physiological processes and may also be involved in the maintenance of pathological conditions (Kampinga and Garrido 2012). HSPB1 is usually overexpressed in various tumors and cancer cell lines. Depending on the tumor type, its increased expression was either associated with a good or poor prognosis or had no prognostic value (Kaigorodova and Bogatyuk 2014).

Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease (Almeida-Souza L et al. 2010) and distal hereditary motor neuropathy. Related signaling pathways include regulation of activated PAK-2p34 by proteasome-mediated degradation and signaling by VEGF.

1. Almeida-Souza L et al. (2010) Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-Tooth neuropathy. J Biol Chem 285:12778-12786.
2. Rogalla T et al. (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem 274:18947-18956.

3. Scieglinska D et al. (2019) Heat shock proteins in the physiology and pathophysiology of epidermal keratinocytes. Cell Stress Chaperones 24:1027-1044.