Hsp110 chaperones control client fate determination in the hsp70-Hsp90 chaperone system.

Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the precise roles Sse1 plays in client maturation through the Hsp70-Hsp90 chaperone system are not fully understood. We find that upon pharmacological inhibition of Hsp90, a model protein kinase, Ste11DeltaN, is rapidly degraded, whereas heterologously expressed glucocorticoid receptor (GR) remains stable. Hsp70 binding and nucleotide exchange by Sse1 was required for GR maturation and signaling through endogenous Ste11, as well as to promote Ste11DeltaN degradation. Overexpression of another functional NEF partially compensated for loss of Sse1, whereas the paralog Sse2 fully restored GR maturation and Ste11DeltaN degradation. Sse1 was required for ubiquitinylation of Ste11DeltaN upon Hsp90 inhibition, providing a mechanistic explanation for its role in substrate degradation. Sse1/2 copurified with Hsp70 and other proteins comprising the "early-stage" Hsp90 complex, and was absent from "late-stage" Hsp90 complexes characterized by the presence of Sba1/p23. These findings support a model in which Hsp110 chaperones contribute significantly to the decision made by Hsp70 to fold or degrade a client protein.

Development of a conceptual model for mass gatherings

In making the arrangements for the visit of Pope John Paul II to San Antonio, Texas, in September, 1987, it was discovered that no comprehensive documents or guidelines are available in the public sector for planning such an event. It was not clear which, if any, laws applied. The literature describes rock concerts, papal masses, and civil disorders. These events are held in stadia, and in the open. There was little agreement on what services, if any, were needed to protect the public's health and the environment; or if needed, how services should be provided, or by whom.^ A literature review and bibliography are given to provide greater understanding of the variety of mass gatherings and the many factors that impinge on temporary groups while away from their homes. Descriptions of past mass gatherings in terms of personnel ratios are provided. This study develops a conceptual model which delineates some of the known parameters necessary for successfully conducting a mass gathering. A study of one such site is given.^ Provisions for public wellness and freedom from disease at a mass gathering include adequate water (fluids), food, sanitary facilities, security, transportation, and medical services. The determination of adequacy of these provisions is discussed. Methods of determining the use of provided facilities are given. ^