Molecular Analysis of Proteins Involved in Human Disease 
lator of diabetes in RIPHA-33 mice and that the 
sex bias may reflect a decreased ability of male 
mice to control their blood glucose levels. 
Current studies focus on a comparison of the 
RIPHA model with mice of the non-obese dia- 
betic (NOD) line and on the role played by cyto- 
kines, such as interleukin-1 , tumor necrosis fac- 
tor, interferon-7, and interleukin-6, during the 
progression of the disease. 
Folding and Assembly 
of the Tumor-Suppressor Protein p53 
Until recently it was widely assumed that the 
folding and oligomerization of newly synthesized 
polypeptides and their subsequent molecular re- 
arrangements are spontaneous processes that do 
not require the intervention of other cellular pro- 
teins. However, it is now apparent that members 
of the stress-70 protein family are "chaperones" 
intimately involved in facilitating protein folding 
and assembly within prokaryotic and eukaryotic 
cells. 
Our previous studies of the interaction of BiP, 
the endoplasmic reticulum stress-70 protein, 
with newly synthesized membrane and secretory 
proteins has led to an understanding of the role of 
stress-70 proteins in stabilizing unfolded or 
partly folded polypeptides in a form competent 
for further folding and oligomeric assembly. 
Current studies focus on the role of hsc70, the 
cytosolic stress-70 protein, in modulating the 
structure or activity of mutant forms of the 
tumor-suppressor protein p53. 
Other workers have shown that p53 plays a 
role in regulation of normal cell growth and that 
it binds to a number of viral-transforming pro- 
teins, including SV40 T antigen. Mutations in p53 
convert the protein to an oncogenic form capable 
of co-operating with another oncogene, activated 
ras, to transform cells. These mutant forms of 
p53 appear to be altered conformationally, as in- 
dicated by loss of T antigen recognition, altered 
reactivity with monoclonal antibodies, and co- 
translational binding to hsc70. We are analyzing 
the interaction between p53 and hsc70, using the 
fd bacteriophage expression system. By screening 
p53-peptide-expressing bacteriophage for bind- 
ing to hsc70, with subsequent enrichment and 
amplification in bacteria of those expressing 
hsc70-binding epitopes, the region(s) in p53 rec- 
ognized by hsc70 will be identified. 
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