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Stress-Induced Expression of a Novel Variant of Human Fumarate Hydratase (FH)

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Fumarate hydratase (FH) is an enzyme of the mitochondrial tricarboxylic acid cycle (TCAC). Here we report the characterization of a novel FH variant (FHv) that contains an alternative exon 1b, thus lacking the mitochondrial signal sequence. Distinct from mitochondrial FH, FHv localized to cytosol and nucleus and lacked FH enzyme activity. FHv was expressed ubiquitously in human fetal and adult tissues. Heat shock and prolonged hypoxia increased FHv expression in a cell line (HTB115) by nine- and fourfold, respectively. These results suggest that FHv has an alternative function outside the TCAC related to cellular stress response.
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Keywords: Alternative exon; Fumarate hydratase (FH); Heat shock; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hypoxia; Stress; Tricarboxylic acid cycle (TCAC)

Document Type: Research Article

Affiliations: 1: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 2: National Public Health Institute, Department of Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland

Publication date: February 1, 2007

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  • Gene Expression The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.

    From Volume 16, Gene Expression The Journal of Liver Research is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

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