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J Visvader

Publications and source records attributed to J Visvader.

22 records · Page 2Linked to original sources
PubMed1989

fos-jun Conspiracy: implications for the cell.

Two nuclear oncoproteins, fos and jun (AP-1), cooperate in forming a very stable heterodimeric complex that binds to the AP-1 site with increased affinity. The 'leucine zipper' domain of both fos and jun is necessary for the formation of this heterodimer. Mutations of single residues within the leucine zipper domain had no effect on protein complex formation. However, mutagenesis of the first leucine of the heptad repeat in either fos or jun basic regions and alteration of the spacing between the basic and leucine zipper domains indicate that the basic region of fos has a crucial role in determining the DNA binding affinity of the transcriptional complex. Mutations of the basic amino acids in fos protein prevent binding to TPA (phorbol ester)-responsive element (TRE) in the presence of wild-type jun protein. Thus fos protein appears to be dominant in jun-fos binding to DNA, even though fos alone cannot bind to TRE. Mutants in the basic regions of fos and jun can be exploited as dominant-negative mutants to ablate their normal cellular function.

Amino Acid Sequence↗
PubMed1988

Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes.

Protooncogene fos is rapidly and transiently induced by nerve growth factor (NGF) in rat pheochromocytoma PC12 cells. Two adjacent promoter elements have been identified to mediate the NGF response. One element colocalizes with the serum response element (SRE) centered at position -308, previously shown to confer inducibility by serum, phorbol 12-myristate 13-acetate, and epidermal growth factor, whereas the other element, termed SRE-2, maps approximately 20 base pairs downstream of the SRE and contains several sequence repeats. This element also confers serum responsiveness. Gel mobility shift assays have demonstrated that there are specific nucleoprotein complexes associated with each element and that these exist in the cell prior to NGF induction. The NGF response is independent of the cAMP-regulatory element(s) and does not require cAMP-dependent protein kinase II, as induction by NGF is retained in the mutant PC12 cell line A126-1B2. Finally, the human heat shock HSP70 promoter is also transcriptionally activated by NGF and appears to bind the same nuclear complex as the SRE-2 element of the c-fos promoter.

Animals↗
PubMed1988

Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element.

Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells (PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position -60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE), is sufficient to confer cAMP responsiveness to a herpes thymidine kinase/CAT fusion gene. The specific binding of a nuclear protein to the c-fos CRE can be competed by the somatostatin and alpha-chorionic gonadotropin (alpha-CG) promoter regions that contain CREs. Gel mobility shift assays with double-stranded oligonucleotides containing either the wild-type or mutated c-fos CRE sequence have demonstrated that binding occurs only to the wild-type CRE. The nuclear factor binding to the c-fos CRE is likely to be transcription factor CREB (CRE nuclear binding protein), because an affinity-purified 43-kD CREB isolated from PC12 cells binds efficiently in a DNA footprinting assay. Thus, regulation of the c-fos gene transcription appears to involve a mechanism common to many genes that respond to cAMP as a second message leading to cell growth and differentiation.

Adenylyl Cyclases↗