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

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Abstract:

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.

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

DOI: http://dx.doi.org/10.3727/105221607783417592

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 covers all aspects of the gene including transcriptional and epigenetic control mechanisms, microRNAs, RNA processing, molecular mechanism of cellular differentiation, growth and development, translational and posttranslational mechanisms.

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