Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

In addition to being potent chaperones that protect cells against the accumulation of unfolded proteins under stress conditions, mammalian small heat shock proteins (small Hsps) regulate many vital cellular processes in normal and pathological cells. Indeed, these Hsps are constitutively expressed in many tissues and show dramatic changes in their levels of expression in most human pathologies. They are characterized by a large spectrum of activities and are particularly active in protein conformational and inflammatory diseases as well as in cancer pathologies. It is now believed that the immense cellular implications of small Hsps results from their ability to interact, through particular structural changes, with many different client proteins that are subsequently modulated in their activities or half-lifes. Here, we have integrated functionally and structurally the recent data in the literature concerning the interactions of mammalian small Hsps with specific clients. Further analysis with geneMANIA software and database confirmed the incredibly large number of functions associated with these Hsps. The consequences for human pathologies as well as putative therapeutic strategies are discussed, particularly when the expression of small Hsps is harmful (as in some cancer pathologies) or when it appears beneficial for patients.