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Molecular and Cellular Biology, November 2000, p. 8420-8431, Vol. 20, No. 22
Dana-Farber Cancer Institute and Harvard
Medical School, Boston, Massachusetts 02115,1
and Department of Biochemistry, St. Jude Children's
Research Hospital, Memphis, Tennessee 381052
Received 15 June 2000/Returned for modification 22 August
2000/Accepted 1 September 2000
One consequence of transforming growth factor
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
p53 Binds Selectively to the 5' Untranslated Region of
cdk4, an RNA Element Necessary and Sufficient for
Transforming Growth Factor
- and p53-Mediated Translational
Inhibition of cdk4


(TGF-
)
treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show that the 5' untranslated region (UTR) of the cdk4 mRNA is both necessary and sufficient
for wild-type p53-dependent TGF-
-regulated translational inhibition
of cdk4. Wild-type p53 bound selectively to the 5' UTR of
the cdk4 mRNA and inhibited translation of RNAs that
contain this region. RNA binding and translational control
are two genetically separable functions of p53, as are specific and
nonspecific RNA binding. Moreover, transactivation-defective mutants of
p53 retain the ability to regulate cdk4 translation. Our
findings suggest that p53 functions as a regulator of translation in
response to TGF-
in vivo.
*
Corresponding author. Mailing address: Dana-Farber
Cancer Institute and Harvard Medical School, 44 Binney St., Boston, MA 02115. Phone: (617) 632-2206. Fax: (617) 632-5417. E-mail:
mark_ewen{at}dfci.harvard.edu.
Present address: Cancer Biology Program, Division of
Hematology-Oncology, Department of Medicine, Beth Israel Deaconess
Medical Center and Harvard Medical School, Boston, MA 02215.
Present address: Department of Biochemistry, Faculty of Science,
Mahidol University, Bangkok 10400, Thailand.
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