Hypoxic regulation of glutamine metabolism through HIF1 and SIAH2 supports lipid synthesis that is necessary for tumor growth.
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ABSTRACT:
SUBMITTER: Sun RC
PROVIDER: S-EPMC3920584 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
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Hypoxic regulation of glutamine metabolism through HIF1 and SIAH2 supports lipid synthesis that is necessary for tumor growth.
Sun Ramon C RC Denko Nicholas C NC
Cell metabolism 20140201 2
Recent reports have identified a phenomenon by which hypoxia shifts glutamine metabolism from oxidation to reductive carboxylation. We now identify the mechanism by which HIF-1 activation results in a dramatic reduction in the activity of the key mitochondrial enzyme complex α ketoglutarate dehydrogenase (αKGDH). HIF-1 activation promotes SIAH2 targeted ubiquitination and proteolysis of the 48 kDa splice variant of the E1 subunit of the αKGDH complex (OGDH2). Knockdown of SIAH2 or mutation of th ...[more]
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