Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Modulation of MLC-2v gene expression by AP-1: complex regulatory role of Jun in cardiac myocytes. 1126 56

Osteopontin (OPN) expression increases in the heart during hypertrophy and heart failure. Here, we studied the role of OPN in pressure overload-induced hypertrophy and analyzed the signaling pathways involved in hypertrophy. Aortic banding (AB) was performed in a group of wild-type (WT) and OPN knockout (KO) mice to induce pressure overload. Left ventricular (LV) structural and functional remodeling was studied 1 month after AB. AB increased OPN and beta1 integrin (a receptor for OPN) protein expression in WT-AB group. Hypertrophic response as measured by increased heart weight-to-body weight ratio and myocyte cross-sectional area was significantly increased in WT-AB and KO-AB groups when compared with their respective shams. However, the increase was significantly higher in WT-AB. Re-expression of atrial natriuretic factor was only detected in WT-AB group. LV end-diastolic pressure-volume curve obtained using Langendorff perfusion analysis exhibited a leftward shift in WT-AB group, not in KO-AB. LV-developed pressures measured over a range of LV volumes were significantly increased in WT-AB, not in KO-AB mice. Increased phosphorylation of c-Jun N-terminal kinases, p38 kinase, Akt, and glycogen synthase kinase-3beta was significantly higher in WT-AB when compared with KO-AB group. Increased OPN expression may play an essential role in modulating compensatory cardiac hypertrophy in response to chronic pressure overload.
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PMID:Osteopontin modulates myocardial hypertrophy in response to chronic pressure overload in mice. 1552 Feb 99