Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D03574 (CoCl2)
 1,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cobalt is often used as a hypoxia mimic in cell culture, because it stabilizes the alpha subunits of the transcription factor, HIF (hypoxia-inducible factor). We have previously shown that HIF stabilization due to a deficiency of the von Hippel Lindau protein (pVHL) in clear cell renal carcinoma (CRCC) was correlated to a down-regulation of oxidative phosphorylation. To better understand this mechanism, we have used CoCl2 in CRCC expressing stably transfected vhl. We show that, in addition to its effect on HIF-alpha subunits, CoCl2 prevented the normal processing of the precursor of cytochrome c oxidase (COX) subunit 4 and induced COX degradation very likely by inhibiting the mitochondrial intermediate peptidase (MIP) that cleaves the COX4 precursor protein. This cobalt-induced MIP inhibition was however not observed in other human mitochondrial precursor sequences as previously predicted from comparison between human and yeast mitochondrial precursor sequences.
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PMID:Inhibition of cytochrome c oxidase subunit 4 precursor processing by the hypoxia mimic cobalt chloride. 1664 49