Modulation of MLC-2v gene expression by AP-1: complex regulatory role of Jun in cardiac myocytes.
Hypertrophic stimulation of cardiac myocytes results in rapid induction of a number of transcription factors, including members of the AP-1 family, which is followed by a programmed alteration in the pattern of gene expression. In the ventricular cardiocytes there is re-expression of the fetal atrial natriuretic factor (ANF) gene and upregulation of its myosin light chain-2 (MLC-2v). The mechanism(s) by which the induction ofAP-1 is coupled to the promoters of these target genes is largely unknown. In this report, we demonstrate that in transient co-transfection assay, c-Jun inhibited while Jun B stimulated the MLC-2v promoter activity. Mutant c-Jun recombinants, in which the activation domains were deleted, still remained inhibitory, but a specific mutation in the leucine zipper, which changes the alignment of Jun with its dimerization partner, caused a reversal of its effect on the target MLC-2v promoter. Based on these findings, we propose that in chicken cardiac myocytes, the regulation of MLC-2v promoter by Jun may occur via its interaction with other proteins, possibly of the leucine zipper family.
Center for Cardiovascular and Muscle Research and the Department of Anatomy and Cell Biology, State University of New York Health Science Center at Brooklyn, 11203, USA.
S K
SK
Goswami
S
S
Shafiq
M A
MA
Siddiqui
D000818:Animals; D024722:Cardiac Myosins; D002478:Cells, Cultured; D002642:Chick Embryo; D019281:Dimerization; D005786:Gene Expression Regulation; D016758:Genes, jun; D016350:Leucine Zippers; D009154:Mutation; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection
D018994:Myosin Light Chains; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C107184:myosin light chain 2; D024722:Cardiac Myosins