title: c-Maf, the gammaD-crystallin Maf-responsive element and growth factor regulation.
abstract: The transcription factor c-Maf has been suggested to regulate the activity of gamma-crystallin promoters in lens fibre cells. We here show that the transactivation potential of c-Maf and MafB for the rat gammaD-crystallin Maf-responsive element (gammaD MARE) is dependent upon the cellular context and, using chimeric and single domain mutants, that c-Maf is most likely to be the cognate factor for the gammaD MARE in the lens. Transactivation of the gammaD MARE by c-Maf in lens cells was not enhanced by c-Fos or c-Jun and was not blocked by dominant negative c-Fos or c-Jun constructs. c-Maf can activate the gammaD MARE as a homodimer since activation of the gammaD-crystallin promoter in P19 embryonic carcinoma cells required only c-Maf, but none of a number of c-Fos and c-Jun family members tested. Transactivation by c-Maf was inhibited by activation of protein kinase A (PKA) (by signal transduction agonist forskolin) or of protein kinase C (PKC) (by signal transduction agonist tetradecanoyl phorbol acetate). Site-directed mutagenesis showed that this effect is not mediated by phosphorylation of the consensus PKA/PKC site in the extended DNA-binding domain, but likely involves activation of MAP kinase kinase, as inhibition by PD98059 increased transactivation by c-Maf.
authors.affiliation: Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands.
authors.forename: Azem
authors.initials: A
authors.lastname: Civil
authors.forename: Siebe T
authors.initials: ST
authors.lastname: van Genesen
authors.forename: Nicolette H
authors.initials: NH
authors.lastname: Lubsen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D030161:Avian Proteins; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003459:Crystallins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D017930:Genes, Reporter; D006133:Growth Substances / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000378:metabolism; D050977:Maf Transcription Factors; D051258:MafB Transcription Factor; D015513:Oncogene Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051257:Proto-Oncogene Proteins c-maf; D051381:Rats; D020218:Response Elements; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D030161:Avian Proteins; D003459:Crystallins; D004268:DNA-Binding Proteins; D006133:Growth Substances; C111440:L-MAF protein, Gallus gallus; D050977:Maf Transcription Factors; C495609:Maf protein, rat; D051258:MafB Transcription Factor; C490405:Mafb protein, rat; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors