title: Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid.
abstract: Terminal differentiation of hematopoietic cells follows a precisely orchestrated program of transcriptional regulatory events at the promoters of both lineage-specific and ubiquitous genes. Here we show that the transcription factor ATF2 is associated with the induction of granulocytic differentiation, and the molecular interaction of ATF2 with a tissue-specific coactivator activating signal cointegator-2 (ASC-2) potentiates the differentiation procedure. All-trans retinoic acid (RA) induced the phosphorylation and expression of ATF2 in the early and middle phase of granulocyte differentiation, respectively. The activation of granulocyte-specific gene expression is increased with the concerted action of another basic regionleucine zipper factor, CCAAT/enhancer-binding protein (C/EBPalpha), and ASC-2, which function in a cooperative manner. The interaction between ATF2 and C/EBPalpha in RA-treated cells was enhanced by the ectopic expression of ASC-2. ATF2-mediated transactivation was also increased by co-transfection of ASC-2. This resulted from the direct protein interaction that the N-terminal transactivation domain of ATF2 interacts with the central region of ASC-2. Furthermore, the molecular interaction of ATF2 and ASC-2 was stimulated by RA treatment and inhibited by p38beta kinase inhibitor. Taking these results together, these results suggest that the differentiation-dependent expression and phosphorylation of ATF2 protein physically and functionally interacts with C/EBPalpha and coativator ASC-2 and synergizes to induce target gene transcription during granulocytic differentiation.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Korea.
authors.forename: SunHwa
authors.initials: S
authors.lastname: Hong
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Choi
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Yoon Ha
authors.initials: YH
authors.lastname: Choi
authors.forename: Hyung Hoi
authors.initials: HH
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: JaeHun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D051698:Activating Transcription Factor 2; D020816:Amino Acid Motifs; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D005982:Glutathione Transferase / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009154:Mutation; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D020798:Two-Hybrid System Techniques; D020298:U937 Cells
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D022763:CCAAT-Enhancer-Binding Protein-alpha; D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D014157:Transcription Factors; D014212:Tretinoin; D008156:Luciferases; D005982:Glutathione Transferase; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases