title: A LIM protein, Hic-5, functions as a potential coactivator for Sp1.
abstract: Hic-5 is a LIM protein with striking similarity to paxillin, and shuttles between focal adhesions and the nucleus. Our previous study suggested that Hic-5 participates in the transcriptional control of several genes such as the c-fos and p21 genes. In the present study, we examined the function of Hic-5 in the nucleus using the transcriptional promoter region of the p21 gene. When localized to the nucleus, Hic-5 was found to transactivate the p21 promoter through two of five Sp1 sites in the region proximal to the TATA box. The Hic-5 effect was mediated by a transactivation domain of Sp1 and functional interaction with p300 through the LIM4 domain. Hic-5 was also shown to interact functionally and physically with Smad3 through the LIM domains and to potentiate p21 promoter activity together with Smad3 and Sp1. These properties were confirmed in an artificial system using GAL4-fusion protein. Thus, Hic-5 was suggested to have a potential function as a cofactor in the transcriptional complex that contains Sp1, playing a role in gene transcription in the nucleus as well as in integrin signaling at focal adhesion sites.
authors.affiliation: Department of Microbiology, Showa University School of Pharmaceutical Sciences, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Shibanuma
authors.forename: Joo-ri
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nose
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050881:E1A-Associated p300 Protein; D040461:Gene Components / Q000235:genetics; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D060588:LIM Domain Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019913:Nuclear Localization Signals / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D051900:Smad3 Protein; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016329:Sp1 Transcription Factor; C090090:Tgfb1i1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)