Transcriptional activation of the cyclin-dependent kinase inhibitor p21 by PML/RARalpha.

Yang, W L; Zeng, Y X; El-Deiry, W S; Nason-Burchenal, K; Dmitrovsky, E; Chin, K V

Yang, W L; Zeng, Y X; El-Deiry, W S; Nason-Burchenal, K; Dmitrovsky, E; Chin, K V.

Afiliación

Yang WL; Department of Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick 08901, USA.

Mol Cell Biol Res Commun ; 1(2): 125-31, 1999 May.

Article en En | MEDLINE | ID: mdl-10356361

RESUMEN

Acute promyelocytic leukemia (APL) is a result of clonal expansion of hematopoietic precursors blocked at the promyelocytic stage and is associated with a t(15;17) chromosomal translocation and the expression of the PML/RARalpha fusion protein. Treatment of APL cells with retinoic acid (RA) leads to complete remission by inducing growth arrest and differentiation of these cells into granulocytes. The cyclin-dependent kinase inhibitor p21WAF1/CIP1 may be involved in terminal differentiation associated growth arrest. We showed in this study that PML/RARalpha increased the transcription of p21WAF1/CIP1 gene and the activation was further induced by RA treatment. Deletion analysis revealed a region upstream of the p21WAF1/CIP1 promoter that is required for transactivation by PML/RARalpha. Transient transfection of PML/RARalpha in cells increased the endogenous p21WAF1/CIP1 protein levels. These results suggest that the induction of APL cells differentiation by RA may be a result of the activation of p21WAF1/CIP1 by PML/RARalpha.

Asunto(s)

Quinasas Ciclina-Dependientes/antagonistas & inhibidores; Ciclinas/metabolismo; Proteínas de Neoplasias/fisiología; Proteínas Nucleares; Receptores de Ácido Retinoico/fisiología; Factores de Transcripción/fisiología; Extractos Celulares; Inhibidor p21 de las Quinasas Dependientes de la Ciclina; Ciclinas/genética; Células HL-60; Células HeLa; Humanos; Inmunohistoquímica; Proteínas de Neoplasias/metabolismo; Regiones Promotoras Genéticas; Proteína de la Leucemia Promielocítica; Unión Proteica; Receptores de Ácido Retinoico/metabolismo; Receptor alfa de Ácido Retinoico; Eliminación de Secuencia; Factores de Transcripción/metabolismo; Activación Transcripcional; Transfección; Células Tumorales Cultivadas; Proteínas Supresoras de Tumor

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Ciclinas / Receptores de Ácido Retinoico / Quinasas Ciclina-Dependientes / Proteínas de Neoplasias Límite: Humans Idioma: En Revista: Mol Cell Biol Res Commun Asunto de la revista: BIOLOGIA MOLECULAR Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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