IDH1 and IDH2
IDH1
In databases:
● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery):
3417 or IDH1
● Ensembl (http://www.ensembl.org/index.html):
ENSG00000138413
● GeneCards (http://www.genecards.org/):
IDH1
● HGNC (http://www.genenames.org/): 5382 or IDH1
● Enzyme Number (IUBMB):
EC 1.1.1.42
Gene locus :
2q33.3
Protein name:
Isocitrate dehydrogenase 1 (NADP+),
soluble
Protein Size:
414 amino acids; about 47 kDa
IDH2
In
databases:
● Ensembl (http://www.ensembl.org/index.html):
ENSG00000182054
● HGNC (http://www.genenames.org/): 5383 or IDH2
● Enzyme Number (IUBMB):
EC 1.1.1.42
Gene locus:
15q26.1
Protein name:
Isocitrate dehydrogenase 2 (NADP+), mitochondrial
Protein Size:
452 amino acids; about 51 kDa
Function:
Isocitrate dehydrogenases catalyze the
oxidative decarboxylation of isocitrate to 2-oxoglutarate. IDH1 localizes to
the cytoplasm and peroxisomes, and acts as a NADP-dependent protein that
catalyzes decarboxylation of isocitrate into alpha-ketoglutarate. The
homologous isocitrate dehydrogenase 2 (IDH2) is the only protein homologous to
IDH1 that also utilizes NADP; however IDH2 localizes to the mitochondria. IDH2
plays an important role in controlling the mitochondrial redox balance, and in
providing protection from oxidative damage similar to IDH1.
Cancer-related alterations:
Several recent studies have identified a
genetic alteration in the IDH1 or IDH2 genes of malignant brain tumors. While
IDH1 or IDH2 mutations are observed in the majority of grade II and III
astrocytomas and oligodendrogliomas, glioblastomas and low grade astrocytic
tumors demonstrate an absence or low frequency of mutations.
All IDH alterations are point mutations
resulting in a “missense” change at codon 132 of IDH1, and codons 140 or 172 of
IDH2. Residues 132 of IDH1 and 172 of IDH2 are analogous between genes, and
occur in exon 4 at a highly conserved region of the isocitrate binding site.
The mutation is thought to down-regulate or even eliminate enzyme activity,
leading to increased cellular oxidative stress and damage.
IDH1 or IDH2 mutations have also been
observed in about 10% of acute myeloid leukemia (AML) cases.
References (open access):
Isocitrate dehydrogenase 1 and 2 mutations in cancer:
alterations at a crossroads of cellular metabolism. Reitman ZJ, Yan H. J Natl
Cancer Inst. 2010 Jul 7;102(13):932-41.
Mutant metabolic enzymes are at the origin of gliomas.
Yan H, Bigner DD, Velculescu V, Parsons DW. Cancer
Res. 2009 Dec 15;69(24):9157-9.
Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH
mutations in glioblastoma. Krell D, Assoku M, Galloway M, Mulholland P,
Tomlinson I, Bardella C. PLoS One. 2011;6(5):e19868.
IDH1 and IDH2 mutations in myeloid neoplasms--novel
paradigms and clinical implications. Cazzola M. Haematologica. 2010
Oct;95(10):1623-7.
IDH1 and IDH2 gene mutations identify novel molecular
subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer
and Leukemia Group B study. Marcucci G, Maharry K, Wu YZ, Radmacher MD, Mrózek
K, Margeson D, Holland KB, Whitman SP, Becker H, Schwind S, Metzeler KH, Powell
BL, Carter TH, Kolitz JE, Wetzler M, Carroll AJ, Baer MR, Caligiuri MA, Larson
RA, Bloomfield CD. J Clin Oncol. 2010 May 10;28(14):2348-55.
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