title: MAP kinase additively activates the mouse Per1 gene promoter with CaM kinase II.
abstract: In a previous study, we showed that the Ca2+/calmodulin-dependent protein kinase IIdelta (CaMKIIdelta) activates the mouse Per1 (mPer1) promoter through a 5'-GAGGGG-3' motif near exon1B. Here we use luciferase reporter gene assays to document additive activation of the mPer1 promoter by CaMKIIdelta and mitogen-activated protein kinase (MAPK) pathways. Transfection of constitutively active MEKK markedly increased mPer1 promoter activity in NB2A cells. Experiments using MAPK inhibitors and dominant-negative c-Jun NH2-terminal kinase 1 (JNK1) showed that extracellular signal-regulated kinase (ERK) accounts for MEKK-induced mPer1 gene activation. We next defined the ERK-responsive region in the mPer1 promoter. A region from -1735 to -1721 was required for ERK-induced promoter activation. We also identified a CaMKII-responsive element near exon 1B. Although mutation of the CaMKII-responsive element has no effect on the ERK responsiveness, elimination of a GC-rich sequence downstream of the CaMKII-responsive region totally abolished ERK responsiveness. Finally, ERK-induced promoter activation was additively potentiated by co-transfection with active CaMKIIdelta. These results suggest that additive activation by ERK and CaMKII, most likely as a result of photic stimulation in the suprachiasmatic nucleus, plays a critical role in activating the mPer1 gene promoter.
authors.affiliation: Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nomura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517673:Camk2d protein, mouse