| General information | Literature | Expression | Regulation | Mutation | Interaction |
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Basic Information |
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|---|---|
Gene ID | 3417 |
Name | IDH1 |
Synonymous | HEL-216|HEL-S-26|IDCD|IDH|IDP|IDPC|PICD;isocitrate dehydrogenase 1 (NADP+), soluble;IDH1;isocitrate dehydrogenase 1 (NADP+), soluble |
Definition | NADP(+)-specific ICDH|NADP-dependent isocitrate dehydrogenase, cytosolic|NADP-dependent isocitrate dehydrogenase, peroxisomal|epididymis luminal protein 216|epididymis secretory protein Li 26|isocitrate dehydrogenase [NADP] cytoplasmic|oxalosuccinate deca |
Position | 2q33.3 |
Gene type | protein-coding |
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Title |
Abstract |
| Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. | Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown. We have shown that tumor-derived IDH1 mutations impair the enzymes affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, alpha-ketoglutarate (alpha-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by alpha-KG. The rise in HIF-1alpha levels was reversible by an alpha-KG derivative. HIF-1alpha levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway. |