| First Author | Tao H | Year | 1999 |
| Journal | DNA Cell Biol | Volume | 18 |
| Issue | 1 | Pages | 75-84 |
| PubMed ID | 10025511 | Mgi Jnum | J:52571 |
| Mgi Id | MGI:1329771 | Doi | 10.1089/104454999315646 |
| Citation | Tao H, et al. (1999) Reciprocal regulation of gadd45 by C/EBP alpha and c-Myc. DNA Cell Biol 18(1):75-84 |
| abstractText | 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/EBP alpha suppresses mitotic growth. We report here that C/EBP alpha directly regulates gadd45 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/EBP alpha-mediated transactivation and impaired binding of C/EBP alpha in adipocyte nuclear extracts. We also found that c-Myc antagonized C/EBP alpha-mediated transactivation of gadd45. Analysis of systematically altered forms of C/EBP alpha revealed that c-Myc antagonism targeted the antimitotic, transcriptional activation domain of C/EBP alpha. In addition, we localized the regulatory sequences in the gadd45 promoter that are required for c-Myc antagonism of C/EBP alpha transactivation. Our findings reveal that C/EBP alpha 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/EBP alpha and c-Myc in 3T3-L1 cells includes antagonistic transcriptional control of a growth-arrest-associated gene. |
