HSP27: History
The great discovery of Heat Shock Proteins occurred at the International Institute of Genetics and Biophysics in Naples at the laboratory of Ferruccio Ritossa in 19628. By chance, and as it may occur just very few times during the life of an investigator, Ritossa was working on nucleic acid synthesis in puffs of Drosophila salivary glands. Unexpectedly, he noticed new chromosomal puffs when cells were placed at higher temperatures than normal conditions9. Today, this is identified as the heat shock response which is a universal response to a great variety of stresses. Twelve years later, Alfred Tissières discovered that the Heat Shock Proteins play a role in the protection from these insults10.
Figure 1. (click image for larger version)
Moreover, heat shock proteins have been identified in many other cellular functions like chaperoning of misfolded proteins and thus denominated as “Molecular Chaperones”. More recently, Heat Shock Proteins have been organized into different named families1, and have been linked to several normal and pathological conditions. Small Heat Shock Proteins (sHSP), have been described first in fruit flies Drosophila Melanogaster as being expressed together with high molecular masses heat shock proteins in cells exposed to a heat treament11. At the molecular level, sHSPs are characterized in their C-terminal moiety by a conserved sequence (the alpha-crystallin domain) shared by mammalian α-crystallin polypeptide (Figure 1). sHSP have been described in every eukaryotes studied so far12,4, as well as in prokaryotes. For example, the human genome contains 10 genes encoding different small stress proteins13 (Table 1). Hsp27 and αB-crystallin are characterized by a remarkable variety of cellular functions, the first one being to protect the cell against conditions that would otherwise be lethal to the cell. These sHSPs increase the cellular resistance to different types of stress, including heat shock14, oxidative conditions15,16,17, exposure to cytotoxic drugs13,14 and apoptotic inducers. In vitro analysis has demonstrated that Hsp27 and αB-crystallin share an ATP-independent chaperone activity that counteracts protein denaturation and helps in the refolding of denatured polypeptides. However, a chaperone activity is not shared by all the members of the human sHsp family. Hsp27 is also known to modulate cell growth, differentiation, intracellular redox state5 and tumorigenicity.18-20
