TITLE

Reciprocal Regulation of gadd45 by C/EBPalpha and c-Myc

AUTHOR(S)
Tao, Heng; Umek, Robert M.
PUB. DATE
January 1999
SOURCE
DNA & Cell Biology;Jan1999, Vol. 18 Issue 1, p75
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The CCAAT/enhancer-binding protein-alpha (C/EBP alpha) drives the differentiation of murine 3T3-L1 cells to adipocytes through transcriptional activation of phenotype-associated genes via proximal promoter elements. In addition, C/EBPalpha suppresses mitotic growth. We report here that C/EBP alpha directly regulates gadd 45 through a C/EBP-binding site in the proximal promoter. A 3 basepair substitution, directed at the most conserved residues of the sequence, reduced C/EBPalpha-mediated transactivation and impaired binding of C/EBPalpha in adipocyte nuclear extracts. We also found that c-Myc antagonized C/EBPalpha -mediated transactivation of gadd 45. Analysis of systematically altered forms of C/EBPalpha revealed that c-Myc antagonism targeted the antimitotic, transcriptional activation domain of C/EBPalpha. In addition, we localized the regulatory sequences in the gadd 45 promoter that are required for c-Myc antagonism of C/EBPalpha transactivation. Our findings reveal that C/EBPalpha coordinates cellular differentiation and mitotic growth arrest through direct, coordinate regulation of phenotype-associated and growth-arrest-associated genes. In addition, our findings reveal that the reciprocal relation between C/EBPalpha and c-Myc in 3T3-L1 cells includes antagonistic transcriptional control of a growth-arrest-associated gene.
ACCESSION #
6463017

 

Related Articles

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics