Open Accessp53 Binds Selectively to the 5′ Untranslated Region of cdk4, an RNA Element Necessary and Sufficient for Transforming Growth Factor β- and p53-Mediated Translational Inhibition of cdk4
Author(s) -
Susan J. Miller,
Tuangporn Suthiphongchai,
Gerard P. Zambetti,
Mark E. Ewen
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.22.8420-8431.2000
Subject(s) - biology , translational regulation , untranslated region , transactivation , translation (biology) , three prime untranslated region , eif4e , five prime untranslated region , rna binding protein , microbiology and biotechnology , messenger rna , rna , genetics , gene expression , gene
One consequence of transforming growth factor β (TGF-β) treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show that the 5′ untranslated region (UTR) of thecdk4 mRNA is both necessary and sufficient for wild-type p53-dependent TGF-β-regulated translational inhibition ofcdk4 . Wild-type p53 bound selectively to the 5′ UTR of thecdk4 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 regulatecdk4 translation. Our findings suggest that p53 functions as a regulator of translation in response to TGF-β in vivo.