p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells.
Transcriptional activation of the c-jun gene is a critical event in the differentiation of F9 cells. In our previous studies we characterized an element [differentiation response element (DRE)] in the c-jun promoter that is both necessary and sufficient to confer the capacity for differentiation-dependent up-regulation. This element binds the differentiation regulatory factor (DRF) complex, of which one component is the adenovirus E1A-associated protein p300. We have now identified activation transcription factor-2 (ATF-2) as a DNA-binding subunit of the DRF complex. p300 and ATF-2 interact with each other in vivo and in vitro. The bromodomain and the C/H2 domain of p300 mediate the binding to ATF-2, which in turn requires a proline-rich region between amino acids 112 and 350 for its interaction with p300. The phosphorylation of the serine residue at position 121 of ATF-2 appears to be induced by protein kinase C alpha (PKC alpha) after treatment of cells with retinoic acid (RA) or induction with E1A. In cotransfection assays, wild-type ATF-2 enhanced the transcription of an E2/tk-luciferase construct, in conjunction with p300-E2. However, a mutant form of ATF-2 with a mutation at position 121 (pCMVATF-2(Ser121-Ala)) did not. These results suggest that ATF-2 and p300 cooperate in the control of transcription by forming a protein complex that is responsive to differentiation-inducing signals, such as RA or E1A, and moreover, that the phosphorylation of ATF-2 by PKC alpha is probably a signaling event in the pathway that leads to the transactivation of the c-jun gene in F9 cells.
Kawasaki
H
H
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba 305, Japan.
Song
J
J
Eckner
R
R
Ugai
H
H
Chiu
R
R
Taira
K
K
Shi
Y
Y
Jones
N
N
Yokoyama
K K
KK
D051698:Activating Transcription Factor 2; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral / Q000235:genetics; D016758:Genes, jun / Q000187:drug effects / Q000235:genetics*; D007527:Isoenzymes / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000502:physiology; D051571:Protein Kinase C-alpha; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014212:Tretinoin; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha