Stress-induced expression of a novel variant of human fumarate hydratase (FH).
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 (HTB 115) by nine- and fourfold, respectively. These results suggest that FHv has an alternative function outside the TCAC related to cellular stress response.
Lehtonen
Heli J
HJ
Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Ylisaukko-Oja
Sanna K
SK
Kiuru
Maija
M
Karhu
Auli
A
Lehtonen
Rainer
R
Vanharanta
Sakari
S
Jalanko
Anu
A
Aaltonen
Lauri A
LA
Launonen
Virpi
V
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D018076:DNA, Complementary; D005455:Fluorescent Antibody Technique; D005649:Fumarate Hydratase / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D013312:Stress, Physiological / Q000235:genetics*; D013347:Subcellular Fractions / Q000201:enzymology
D018076:DNA, Complementary; D005649:Fumarate Hydratase