This Article Full Text Full Text (PDF) All Versions of this Article: 1541-7786.MCR-05-0212v1 4/3/177    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santos, C. R. Articles by Lazo, P. A. Search for Related Content PubMed PubMed Citation Articles by Santos, C. R. Articles by Lazo, P. A.

---

Cell Cycle, Cell Death, and Senescence

VRK1 Signaling Pathway in the Context of the Proliferation Phenotype in Head and Neck Squamous Cell Carcinoma

¹ Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Spain; ² Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas; ³ Departamento de Patología, Hospital Universitario 12 de Octubre, Madrid, Spain; ⁴ Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts; and ⁵ Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York

Requests for reprints: Pedro A. Lazo, Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Cientificas, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain. Phone: 34-923-294-804; Fax: 34-923-294-795. E-mail: plazozbi{at}usal.es

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. (Mol Cancer Res 2006;4(3):177–85)

This article has been cited by other articles:

				T.-H. Kang, D.-Y. Park, W. Kim, and K.-T. Kim VRK1 phosphorylates CREB and mediates CCND1 expression J. Cell Sci., September 15, 2008; 121(18): 3035 - 3041. [Abstract] [Full Text] [PDF]

				T.-H. Kang, D.-Y. Park, Y. H. Choi, K.-J. Kim, H. S. Yoon, and K.-T. Kim Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells Mol. Cell. Biol., December 15, 2007; 27(24): 8533 - 8546. [Abstract] [Full Text] [PDF]

				T. Ito Role of Histone Modification in Chromatin Dynamics J. Biochem., May 1, 2007; 141(5): 609 - 614. [Abstract] [Full Text] [PDF]

				A. Valbuena, F. M. Vega, S. Blanco, and P. A. Lazo p53 Downregulates Its Activating Vaccinia-Related Kinase 1, Forming a New Autoregulatory Loop. Mol. Cell. Biol., July 1, 2006; 26(13): 4782 - 4793. [Abstract] [Full Text] [PDF]