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(Received for publication, September 6, 1996, and in revised form, September 23, 1996)
From the Department of Biochemistry, University of Connecticut
Health Center, Farmington, Connecticut 06032
p16INK4 is a specific cyclin
D-dependent kinase inhibitor and a multiple tumor
suppressor. Inactivation of p16 is frequent in both primary tumors and
tumor-derived cell lines. We describe here the conformational
properties and oligomerization state of seven mutant p16 proteins; all
of them are deficient in function. Four of the seven proteins show
significantly disrupted secondary structure and backbone folding. The
other three adopt partially folded, molten globule-like conformations.
These proteins have near-native levels of secondary structure, but lack
the ability to undergo a cooperative thermal transition and are
substantially less resistant to proteolysis than is wild type p16. At
low concentrations, two of the seven proteins are monomers, three
exhibit an apparent molecular weight between the value of a monomer and
a dimer, and the other two aggregate significantly. Our results
strongly suggest that defective protein folding and/or aggregation is a
common mechanism for inactivation of p16.
Volume 271, Number 46,
Issue of November 15, 1996
pp. 28734-28737
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
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