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J Biol Chem, Vol. 274, Issue 29, 20053-20055, July 16, 1999
From the Division of Molecular Pathology, Department of Pathology,
The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205
Oncogenic potential in prostate cancer is
modulated in part by alternative use of genes of the pp32
family. This family includes the tumor suppressor pp32,
expressed in normal tissue, and the pro-oncogenic genes
pp32r1 and pp32r2 that are found principally in
neoplastic cells. At the protein level, pp32, pp32r1, and pp32r2 are
approximately 90% identical, yet they subsume opposite functions. In
this study, we identify the region of pp32 associated with the ability
to inhibit oncogene-mediated transformation in a rat embryo fibroblast
system, an in vitro correlate of tumor-suppressive activity. Deletion and truncation analysis define a region spanning pp32 amino acids 150-174 as absolutely required for inhibition of
transformed foci elicited by RAS and MYC.
Comparison of pp32 with the pp32r1 sequence by moving averages of
sequence identity reveals divergence over this region; pp32r2 also
differs in this region through truncation after pp32 amino acid 131. The deletion experiments and the experiments of nature therefore
converge to demonstrate that tumor-suppressive functions of pp32 reside
in amino acids 150-174. Identification of this minimal
tumor-suppressive region should help elaborate the pathways and
mechanisms through which pp32 family members exert their functions.
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