Small heat-shock protein family: function in health and disease.
In summary, several important issues were discussed at the workshop. These included the importance of oligomer size for different functions of the sHsps, the highly significant observation that the sHsps can block apoptosis; and that some mechanisms of sHsps protection involve glutathione while others may be related to microfilament stability. Further evidence was presented for the chaperone functions of sHsps, and structural studies provided additional information relating sHsps' large oligomeric structure to chaperone function. Regulation of oligomer size by phosphorylation was also a prominent topic of discussion, as was the importance of the relationship of oligomer size to differing functions of Hsp27. An interesting contrast was noted between Hsp27, whose oligomer size is regulated by phosphorylation, and alpha beta-crystallin, whose large oligomer structure is unaffected by phosphorylation. This may prove to be of physiological significance, particularly in cell types that express both of these proteins. Observations of the translocation of MAPKAP kinase 2 from the nucleus to the cytoplasm in live cells suggest that the dynamics of phosphorylation of the sHsps may be more complex than previously thought. One topic that seems to have been settled is that the binding site of at least dimers of sHsps resides in the carboxyl-terminal region of the proteins. Ever-increasing numbers of studies are reporting interesting patterns of sHsp expression, phosphorylation, and subcellular localizations of the sHsps in various cells or tissues in normal and diseased states. Unfortunately, very little is understood about what these observations may mean. It can be expected, however, that as more is learned about the function and regulation of sHsps, the relationships between sHsps and cellular response to disease will become better understood. Lastly, the discovery that specific Hsp27-binding proteins may exist should open completely new avenues of investigation into the functions of sHsps. If the observations of unique subcellular localizations of sHsps in various cells types (e.g., striated muscle and Sertoli cells) can be related to expression of specific Hsp-binding proteins, considerable advances in our understanding of sHsps should result. It was abundantly clear from results presented and from ensuing discussions in the workshop that the study of sHsps is an exceedingly dynamic area of research (FIG. 2) with an ever-expanding significance for a number of other areas of current biological research.
Welsh
M J
MJ
Department of Anatomy and Cell Biology, University of Michigan Medical School, Ann Arbor 48109, USA. welsh@umich.edu
Gaestel
M
M
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger