Stress-70 protein family

It is now realized that members of this family of proteins are present in cells under normal conditions, and that their presence is not strictly stress related. Induction of expression of some members in response to heat shock or other forms of cell stress is only a manifestation of an additional facet of the collective functions of the larger family of proteins. However, for simplicity in nomenclature, I will follow the convention adopted in another recent review and refer to the family of 70-kDa heat-shock-related proteins as the stress-70 protein family (Gethingand Sambrook, 1992). 

Hence, although the specific numerical values reported for ATPase rates of stress-70 proteins show some variation, possibly attributable to differences in specific protein preparation and assay procedures utilized by different individuals, the consensus scheme that these data show is that in the absence of substrate peptide, the stress-70 proteins have a low basal ATPase rate, typically found to be 0.01-0.03 (mol ATP/mol stress-70 protein min). This can be enhanced severalfold either by binding of peptides or denatured proteins, or (as demonstrated by the effect of grpE and dnaJ proteins on dnaK) by the action of ancillary proteins. To the extent that the observations on HSC70 can be generalized to other members of the stress-70 protein family, peptide binding appears to relieve the attenuation of ATPase activity and allow it to proceed at the rate characteristic of the ATPase fragment of the protein alone. 

Pelham, H.R.B. (1990). Functions of the hsp70 protein family An overview. In Stress Proteins in Biology Medicine (Morimoto, R., Tissieres, A., Georgopoulos, C., eds.), pp. 287-300, CSHL Press, Cold Spring Harbor. 

A stressed cell undergoes precise biochemical and morphological changes. General protein synthesis is switched off and a set of specific mRNAs are translated to produce the stress proteins. The intermediate filaments of the cytoskeleton become perinuclear and heat-shock proteins of the 70kDa family are translocated into the nucleus. The 70kDa family appears to play a role in differentiation and development and is crucial to the survival of stressed... 

Other reviews have summarized many of the apparent biological functions of the stress-70 proteins (Craig et ai, 1990, Gething and Sambrook, 1992 Haas, 1991 Winfield and Jarjour, 1991). This review focuses primarily on the protein chemistry and mechanistic enzymology of this protein family. 

Another activity associated with a stress-70 protein is the in vitro disassembly of clathrin cages into triskelions (see Section I V,D). Rothman and colleagues isolated and characterized a protein from bovine brain that facilitated the disassembly of clathrin cages in a reaction that required hydrolysis of ATP they referred to the protein as a clathrin-uncoating ATPase (Schlossman et ai, 1984). Subsequently, it was realized that this protein was a constitutively expressed member of the stress-70 family (HSC70) (Chappell et al 1986). 

Since these early observation on the in vivo modification of stress-70 proteins, there has been further work documenting phosphorylation of several members of the stress-70 family, both in vitro and in vivo, and further exploration of the labeling of BiP by [ Hjadenosine in vivo. However, it is not yet clear what the significance of posttranslational modification of stress-70 proteins may be for regulating their activities. 

Members of the hspVO family of stress proteins bind the GSL 3 sulfogalactosyl ceramide (SGC) (207). The binding site is in the N-terminal ATPase domain (208). Adamantyl SGC, similarly generated via fatty acid replacement, similarly has proven water soluble and is an effective inhibitor of hsp70-SGC binding (200). Adamantyl SGC has been shown to inhibit hsp70 ATPase activity (209) in vitro and therefore may modulate its chaperone function in cells. Such an effect also has therapeutic potential (210). 

Stress/heat shock proteins (see Gagne and Blaise, Chapter 7 of this volume). These constitute a set of protein families of different molecular weights that generally have been referred to as heat shock proteins (HSPs), classified into... 

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