Transcriptional activation of the c-fos gene by a LIM protein, Hic-5.
Hic-5 is a member of LIM family proteins with a striking similarity to paxillin and localizes primarily in the focal adhesion. We recently reported that Hic-5 translocated to the nucleus under oxidative stress and was involved in transcriptional regulation. In the present study, we extended these findings to show that transcription of c-fos gene was up-regulated by overexpression of Hic-5. In clonal stable transformants established from human immortalized fibroblasts by transfection of an expression vector of Hic-5, the constitutive level of c-fos mRNA was well correlated with that of Hic-5. In reporter assays using the luciferase gene under control of the human c-fos 5(')-upstream region from -2.2kb to +1, expression of Hic-5, that was engineered to accumulate in the nucleus, stimulated the transcriptional activity of the c-fos enhancer. From experiments using various deletions and point mutations, it was revealed that multiple sequences including GC/Sp1, Ets, and ERE/AP-1 elements found around the -1.3kb region were responsible for the activation by Hic-5. Hic-5 itself did not bind to these elements in a sequence specific manner, but p300 appeared to be involved in the induction of c-fos. These results suggest that Hic-5 participates in the transcriptional regulation of c-fos as a scaffold in transcriptional complexes.
Kim-Kaneyama
Joo ri
Jr
Department of Microbiology, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.
Shibanuma
Motoko
M
Nose
Kiyoshi
K
D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016762:Genes, fos / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C490351:TGFB1I1 protein, human; C090090:Tgfb1i1 protein, mouse; D015534:Trans-Activators