Stress-induced expression of a novel variant of human fumarate hydratase (FH)

Heli J. Lehtonen; Sanna K. Ylisaukko-Oja; Maija Ht Kiuru; Auli Karhu; Rainer Lehtonen; Sakari Vanharanta; A. N.U. Jalanko; Lauri A. Aaltonen; Virpi Launonen

doi:10.3727/105221607783417592

Stress-induced expression of a novel variant of human fumarate hydratase (FH)

Heli J. Lehtonen, Sanna K. Ylisaukko-Oja, Maija Ht Kiuru, Auli Karhu, Rainer Lehtonen, Sakari Vanharanta, A. N.U. Jalanko, Lauri A. Aaltonen, Virpi Launonen

Research output: Contribution to journal › Article

1 Scopus citations

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 lb, 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.

Original language	English (US)
Pages (from-to)	59-69
Number of pages	11
Journal	Gene Expression
Volume	14
Issue number	2
DOIs	https://doi.org/10.3727/105221607783417592
State	Published - 2007
Externally published	Yes

Keywords

Alternative exon
Fumarate hydratase (FH)
Heat shock
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Hypoxia
Stress
Tricarboxylic acid cycle (TCAC)

ASJC Scopus subject areas

Medicine(all)
Molecular Biology
Genetics

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Lehtonen, H. J., Ylisaukko-Oja, S. K., Kiuru, M. H., Karhu, A., Lehtonen, R., Vanharanta, S., Jalanko, A. N. U., Aaltonen, L. A., & Launonen, V. (2007). Stress-induced expression of a novel variant of human fumarate hydratase (FH). Gene Expression, 14(2), 59-69. https://doi.org/10.3727/105221607783417592

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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 lb, 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)",

author = "Lehtonen, {Heli J.} and Ylisaukko-Oja, {Sanna K.} and Kiuru, {Maija Ht} and Auli Karhu and Rainer Lehtonen and Sakari Vanharanta and Jalanko, {A. N.U.} and Aaltonen, {Lauri A.} and Virpi Launonen",

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journal = "Gene Expression",

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T1 - Stress-induced expression of a novel variant of human fumarate hydratase (FH)

AU - Lehtonen, Heli J.

AU - Ylisaukko-Oja, Sanna K.

AU - Kiuru, Maija Ht

AU - Karhu, Auli

AU - Lehtonen, Rainer

AU - Vanharanta, Sakari

AU - Jalanko, A. N.U.

AU - Aaltonen, Lauri A.

AU - Launonen, Virpi

PY - 2007

Y1 - 2007

N2 - 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 lb, 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.

AB - 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 lb, 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.

KW - Alternative exon

KW - Fumarate hydratase (FH)

KW - Heat shock

KW - Hereditary leiomyomatosis and renal cell cancer (HLRCC)

KW - Hypoxia

KW - Stress

KW - Tricarboxylic acid cycle (TCAC)

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DO - 10.3727/105221607783417592

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