title: Regulation of the human involucrin gene promoter by co-activator proteins.
abstract: Stratified squamous epithelial cells undergo an orderly process of terminal differentiation that is characterized by specific molecular and morphological changes, including expression of the cornified envelope protein involucrin. Significant progress has been made in characterizing the upstream regulatory region of the involucrin gene. Binding sites for AP-1 (activator protein 1) and Sp1 transcription factors were shown to be important for involucrin promoter activity and tissue-specific expression. Defective terminal differentiation is often characterized by decreased or lack of involucrin expression. Recently, a dominant-negative construct of the transcriptional co-activator P/CAF [p300/CBP-associated factor, where CBP stands for CREB (cAMP-response-element-binding protein)-binding protein] was shown to inhibit involucrin expression in immortalized keratinocytes [Kawabata, Kawahara, Kanekura, Araya, Daitoku, Hata, Miura, Fukamizu, Kanzaki, Maruyama and Nakajima (2002) J. Biol. Chem. 277, 8099-8105]. Loss of expression or inactivation of other co-activators has also been demonstrated [Suganuma, Kawabata, Ohshima, and Ikeda (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 13073-13078]. In the present study, we re-expressed CBP and P/CAF in immortalized keratinocyte lines that had lost expression of these co-activator proteins. Re-expression of these proteins restored calcium- and RA (retinoic acid)-responsive involucrin expression in these cells. RA and calcium signalling induced exchange of CBP and P/CAF occupancy at the AP-1 sites of the involucrin promoter. CBP and P/CAF inductions of the involucrin expression were not dependent on MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase), p38, protein kinase C or CaM kinase (calcium/calmodulin-dependent kinase) signalling. Kinase-induced changes in involucrin promoter activity directly resulted from changes in AP-1 protein expression. We concluded that CBP and P/CAF are important regulators of involucrin expression in stratified squamous epithelial cells.
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
authors.forename: Nhu Q
authors.initials: NQ
authors.lastname: Tran
authors.forename: David L
authors.initials: DL
authors.lastname: Crowe
mesh_terms: D016475:3T3 Cells; D000123:Acetyltransferases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D050882:CREB-Binding Protein; D020013:Calcium Signaling / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology; D020218:Response Elements / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection / Q000379:methods; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D011498:Protein Precursors; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C032253:involucrin; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse