title: Extracellular acidification enhances DNA binding activity of MafG-FosB heterodimer.
abstract: Cells are quite sensitive to a change of the extracellular pH and respond to it through detection of the H+/HCO3- level in extracellular fluid. However, little is known about molecular details induced by acidosis, such as intracellular pathways and gene expression. Here we describe properties of gene expression, protein interaction, and DNA binding activity of basic region leucine zipper (bZIP) transcription factor Maf and FosB during extracellular acidification. When cells were incubated with low pH medium, the expressions of small Maf proteins (MafG, MafK, and MafF) and FosB were clearly increased in an extracellular pH-dependent manner and expressed transiently with a peak after 1-2 h after stimulation. Immunofluorescence and protein binding studies indicated that MafG was partially co-localized with FosB in the nucleus and MafG can form heterodimers with FosB at extracellular pH 7.40. Moreover, we found that MafG-FosB complexes are able to bind to AP-1 consensus sequence, TGACTCA. To investigate whether extracellular acidification influences to dimerization and DNA binding activity of MafG and FosB, extracellular pH of cultured cells was decreased from 7.40 to 6.80. The decrease in extracellular pH led to enhanced dimerization of MafG with FosB leading to augmentation of the DNA binding activity of the heterodimer to AP-1 consensus sequence. Moreover, extracellular acidification induces mRNA expression of matrix metalloproteinase-1, one of the genes that are regulated by AP-1. These results suggest that MafG-FosB complexes are involved in transcriptional regulation in response to extracellular acidification.
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan. simokawa@med.gunma-u.ac.jp
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Iku
authors.initials: I
authors.lastname: Kumaki
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Qiu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmiya
authors.forename: Kiyoshige
authors.initials: K
authors.lastname: Takayama
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000143:Acids / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051259:MafG Transcription Factor; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000143:Acids; D004268:DNA-Binding Proteins; C483820:Fosb protein, rat; D051259:MafG Transcription Factor; C491246:Mafg protein, rat; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA; D020781:Matrix Metalloproteinase 1