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Prepublished online as a Blood First Edition Paper on September 4, 2003; DOI 10.1182/blood-2003-06-2091. This Article Full Text (PDF) All Versions of this Article: 2003-06-2091v1 103/1/128    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pipaon, C. Articles by Fernandez-Luna, J. L. Search for Related Content PubMed PubMed Citation Articles by Pipaon, C. Articles by Fernandez-Luna, J. L. Social Bookmarking                   What's this? Submitted June 25, 2003 Accepted August 28, 2003 Jun-N-terminal kinase activity and early growth-response factor-1 gene expression are downregulated in Fanconi anemia group A lymphoblasts Carlos Pipaon, Jose Antonio Casado, Juan Antonio Bueren, and Jose Luis Fernandez-Luna* Unidad de Genetica Molecular, Hospital Universitario Marques de Valdecilla, Santander, Spain Proyecto de Hematopoyesis, Centro de Investigaciones Energeticas Medioambientales y Tecnologicas, Madrid, Spain * Corresponding author; email: fluna{at}humv.es. Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by cellular sensitivity to genotoxic agents. In recent years, FA proteins have been associated with different molecules involved in signal transduction, which has raised the interest on FA-dependent signaling pathways. Here, we report that the c-Jun N-terminal kinase (JNK) fails to phosphorylate in response to UV radiation and treatment with mitomycin C in FA lymphoblast cells derived from type A patients (FA-A). Furthermore, defective kinase activity seems to be specific for JNK as ERK responded to the proper stimuli in FA-A cells. We also demonstrate that the early growth-response factor-1 (Egr-1), a JNK downstream target gene which is normally induced by genotoxic stress, is not upregulated in UV-treated FA-A cells. Moreover, FA-A cells are more sensitive to apoptosis than control lymphoblasts. Both JNK and Egr-1 may be part of a pathway triggered by FA proteins since functional correction of FA-A cells by gene transfer restores, at least in part, JNK activation and Egr-1 expression after UV exposure. Together, our data suggest that activation of JNK and expression of Egr-1 gene in B lymphoblasts mediate a cellular response to genotoxic agents that may be induced by FA proteins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Larder, L. Chang, M. Clinton, and P. Brown Gonadotropin-Releasing Hormone Regulates Expression of the DNA Damage Repair Gene, Fanconi anemia A, in Pituitary Gonadotroph Cells Biol Reprod, September 1, 2004; 71(3): 828 - 836. [Abstract] [Full Text] [PDF]

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