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J Biol Chem, Vol. 275, Issue 20, 15578-15585, May 19, 2000
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From the Expression of heat shock proteins (HSPs) is
controlled by heat shock transcription factors (HSFs). Vertebrates
express multiple HSFs whose activities may be regulated by distinct
signals. HSF3 is specifically activated in unstressed proliferating
cells by direct binding to the c-myb proto-oncogene product
(c-Myb), which plays an important role in cellular proliferation. This
suggests that the c-Myb-induced HSF3 activation may contribute to the
growth-regulated expression of HSPs. Here we report that the p53 tumor
suppressor protein directly binds to HSF3 and blocks the interaction
between c-Myb and HSF3. In addition, p53 stimulates the degradation of c-Myb through a proteasome-dependent mechanism, which is,
at least partly, mediated by induction of Siah in certain types of
cells. Induction of p53 by a genotoxic reagent in DT40 cells disrupts the HSF3-c-Myb interaction and down-regulates the expression of certain
HSPs. Mutated forms of p53 found in certain tumors did not inhibit
c-Myb-induced HSF3 activation. The regulation of HSF3 activity by c-Myb
and p53 sheds light on the molecular events that govern HSP expression
during cellular proliferation and apoptosis.
Laboratory of Molecular Genetics, RIKEN
Tsukuba Life Sciences Center and ¶ Core Research for
Evolutionary Science and Technology Project, Japan Science and
Technology, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan, the
Department of Molecular and Cell Biology, Institute for Frontier
Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8397, Japan,
and the ** Burnham Institute, La Jolla, California 92037

To whom correspondence should be addressed: Lab. of Molecular
Genetics, RIKEN Tsukuba Life Sciences Center, 3-1-1 Koyadai, Tsukuba,
Ibaraki 305-0074, Japan. Tel.: 81-298-36-9031; Fax: 81-298-36-9030; E-mail: sishii@rtc.riken.go.jp.
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