VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma
| Autor: | Sandra Blanco, José Luis Rodríguez-Peralto, Francisco M. Vega, André J. van Wijnen, Alberto Valbuena, Claudio R. Santos, Maria Rodriguez-Pinilla, Ana Sevilla, Montserrat Sanchez-Cespedes, Pedro A. Lazo, Teresa Hernández, Enrique de Alava, Fengzhi Li |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Survivin Cell Cycle Proteins Biology Protein Serine-Threonine Kinases Inhibitor of Apoptosis Proteins Biomarkers Tumor E2F1 Humans Proliferation Marker Promoter Regions Genetic Molecular Biology Cell Proliferation Cyclin-dependent kinase 1 Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 2 Intracellular Signaling Peptides and Proteins Proteins Cell cycle Immunohistochemistry Cell biology Neoplasm Proteins Gene Expression Regulation Neoplastic VRK1 Phenotype Oncology Head and Neck Neoplasms Cancer research biology.protein Carcinoma Squamous Cell Cyclin-dependent kinase 6 Signal transduction Tumor Suppressor Protein p53 Microtubule-Associated Proteins E2F1 Transcription Factor Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1541-7786 |
| Popis: | The vaccinia-related kinase (VRK) proteins are a new family with three members in the human kinome. The VRK1 protein phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. In normal squamous epithelium, VRK1 is expressed in the proliferation area. Because VRK1 can stabilize p53, the expression of the VRK1 protein was analyzed in the context of the p53 pathway and the proliferation phenotype in a series of 73 head and neck squamous cell carcinomas. VRK1 protein level positively correlated with p53 response proteins, particularly hdm2 and p21. The VRK1 protein also correlated positively with several proteins associated with proliferation, such as cyclin-dependent kinase 2 (CDK2), CDK6, cdc2, cyclins B1 and A, topoisomerase II, survivin, and Ki67. The level of VRK1 protein behaves like a proliferation marker in this series of head and neck squamous cell carcinomas. To identify a possible regulatory role for VRK1 and because it regulates gene transcription, the promoters of two genes were studied, CDK2 and SURVIVIN, whose proteins correlated positively with VRK1. VRK1 increases the activity of both the CDK2 and SURVIVIN gene promoters. The expression of VRK1 was analyzed in the context of regulators of the G1-S transition. VRK1 protein levels increase in response to E2F1 and are reduced by retinoblastoma and p16. These data suggest that VRK1 might play a role in cell cycle regulation and is likely to represent the beginning of a new control mechanism of cell cycle, particularly late in the G1-S phase. Fondo de Investigación Sanitaria grant FIS02/0585 (P.A. Lazo); Ministerio de Educación y Ciencia grant SAF2004-02900 (P.A. Lazo); Junta de Castilla y León grants SAN/SA-01/04, SAN/SA-04/05, and CSI05A05 (P.A. Lazo); Fundación de Investigación Médica MM (P.A. Lazo); Ministerio de Ciencia y Tecnología grant SAF2002-01595 (M. Sánchez-Céspedes); Comunidad de Madrid grant CAM 08.1/0032/2003 (M. Sánchez-Céspedes); and Fundación Científica de la Asociación Española contra el Cáncer (F.M. Vega), Fundaçâo para a Ciência e a Tecnologia Portugal (C.R. Santos), Ministerio de Educación y Ciencia (S. Blanco and A. Valbuena), and Consejo Superior de Investigaciones Cientificas predoctoral fellowships (A. Sevilla). |
| Databáze: | OpenAIRE |
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