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.
Goswami
S K
SK
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.
Shafiq
S
S
Siddiqui
M A
MA
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