HSP40: Introduction

The DNAJ/HSP40 family represents a heterogeneous group of co-chaperones characterized by the presence of the remarkably conserved J-domain, responsible for the regulation of the ATPase activity of HSP70s ^1,2,3,4. Based on their architecture, DNAJs/HSP40s are classified in three main subtypes/subfamilies. DNAJs/HSP40s are homodimeric proteins residing in the cytosol of prokaryotes and various subcellular compartments of eukaryotes as well as in the extracellular milieu ^5,6,7,8,9,10. They play essential roles in gene expression and translational initiation, folding and unfolding as well as translocation and degradation of proteins. DNAJs/HSP40s bind to unfolded or non-native polypeptides in order to prevent their aggregation ⁵. Folded proteins are also clients of DNAJs/HSP40s. Their binding mediates the “remodeling” of large multiprotein complexes impacting the balance of protein/protein interactions ⁷. DNAJs/HSP40s are implicated in various human diseases including microbial infections ¹¹, autoimmune diseases ^12,13,14,15, neurodegenerative disorders ^{16, 17}, and cancer ¹⁸. Herein, the diversity of the DNAJ/HSP40 family and its role in disease and therapy is compiled.