Evidence for a function of CtBP in epithelial gene regulation and anoikis.

Grooteclaes, M L; Frisch, S M

Grooteclaes, M L; Frisch, S M.

Afiliación

Grooteclaes ML; The Burnham Institute, La Jolla, California 92037, USA.

Oncogene ; 19(33): 3823-8, 2000 Aug 03.

Article en En | MEDLINE | ID: mdl-10949939

RESUMEN

Previously, we reported that adenovirus E1a protein behaves as a tumor suppressor in human cells. It apparently functions by transcriptionally inducing an array of epithelial cell adhesion genes, while repressing other cell-type specific genes, thus producing an epithelial phenotype. Concomitantly, the cells become sensitive to anoikis (apoptosis of epithelial cells detached from extracellular matrix), potentially causing tumor suppression. E1a protein interacts with the nuclear acetylases p300, CBP and P/CAF, and also with the co-repressor protein CtBP. In this study, we have determined the role of these interactions in E1a's phenotypic effects on human tumor cells. The results indicate that E1a's interaction with CtBP activates at least three epithelial cell adhesion gene promoters. The E-cadherin repressor appeared to be the CtBP-interacting protein delta EF1/ZEB, which bound the ras-repressible E-boxes of the E-cadherin promoter. The E1a-CtBP interaction also contributed to anoikis-sensitization. E1a's interactions with the nuclear acetylases conferred epithelial morphologies but did not activate epithelial genes. These latter interactions did not sensitize tumor cells to anoikis but nevertheless conferred tumor suppression. These results implicate CtBP as an antagonist of the epithelial phenotype and anoikis. They also indicate a new but undefined role for nuclear acetylases in maintaining the transformed phenotype.

Asunto(s)

Proteínas E1A de Adenovirus/metabolismo; Apoptosis; Cadherinas/genética; Proteínas del Citoesqueleto/genética; Proteínas de Unión al ADN/fisiología; Regulación de la Expresión Génica; Fosfoproteínas/fisiología; Factores de Transcripción; Proteínas E1A de Adenovirus/genética; Oxidorreductasas de Alcohol; Línea Celular Transformada; Proteínas de Unión al ADN/metabolismo; Desmoplaquinas; Epitelio/metabolismo; Proteínas de Homeodominio/genética; Proteínas de Homeodominio/metabolismo; Humanos; Proteínas Nucleares/genética; Proteínas Nucleares/metabolismo; Fosfoproteínas/metabolismo; Regiones Promotoras Genéticas; Proteínas Represoras/genética; Proteínas Represoras/metabolismo; Células Tumorales Cultivadas; Homeobox 1 de Unión a la E-Box con Dedos de Zinc; Dedos de Zinc

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Factores de Transcripción / Cadherinas / Regulación de la Expresión Génica / Apoptosis / Proteínas E1A de Adenovirus / Proteínas del Citoesqueleto / Proteínas de Unión al ADN Límite: Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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