title: The regulation of murine H-2Dd expression by activation transcription factor 1 and cAMP response element binding protein.
abstract: Resistance to radiation leukemia virus (RadLV)-induced leukemia is correlated with an increase in H-2Dd expression on the thymocyte surface. It has been shown that elevated H-2Dd expression on infected thymocytes is a result of elevated mRNA transcription and that the transcriptional increase is correlated with elevated levels of a DNA binding activity, H-2 binding factor 1 (H-2 BF1), which recognizes the 5'-flanking sequence (5'-TGACGCG-3') of the H-2Dd gene. Recently, it has been shown that the activation transcription factor 1 (ATF-1) homodimer is one form of the H-2 BF1 complex. Here we demonstrate that the cAMP response element binding protein (CREB) homodimer and the heterodimer of CREB/ATF-1 also recognize the cis regulatory motif and are two additional forms of the H-2 BF1 complex. The levels of mRNA encoding ATF-1 and CREB were both increased in RadLV-infected thymocytes that showed increased levels of H-2 mRNA. Also, all three H-2 BF1 binding activities, ATF-1 homodimer, CREB homodimer, and ATF-1/CREB heterodimer, were increased in RadLV-infected thymocytes that expressed high levels of H-2Dd Ag on the cell surface. Transfection experiments demonstrated that ATF-1 and CREB activated a reporter plasmid containing the H-2 BF1 motif. These observations strongly suggest that both ATF-1 and CREB are involved in the regulation of H-2 gene expression following RadLV infection of mouse thymocytes.
authors.affiliation: Department of Pathology and Kaplan Cancer Center, New York University Medical Center, NY 10016, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ishiguro
authors.forename: G D
authors.initials: GD
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Ishizu
authors.forename: D
authors.initials: D
authors.lastname: Meruelo
mesh_terms: D051697:Activating Transcription Factor 1; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016721:Radiation Leukemia Virus; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D013945:Thymoma / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology
chemical_list: D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens; D014157:Transcription Factors