Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates.

Journal article

In humans both the levels and activity of the alpha-subunit of the hypoxia-inducible transcription factor (HIF-alpha) are regulated by its post-translation hydroxylation as catalyzed by iron- and 2-oxoglutarate (2OG)-dependent prolyl and asparaginyl hydroxylases (PHD1-3 and factor-inhibiting HIF (FIH), respectively). One consequence of hypoxia is the accumulation of tricarboxylic acid cycle intermediates (TCAIs). In vitro assays were used to assess non-2OG TCAIs as inhibitors of purified PHD2...

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Authors: Hewitson, K; Liénard, B; McDonough, M; Clifton, I; Butler, D

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 282
• Issue: 5
• Pages: 3293-3301
• Publication date: 2007-02-01
• DOI: 10.1074/jbc.m608337200
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Breast; Hypoxia-Inducible Factor 1, alpha Subunit; Breast Neoplasms; Citric Acid Cycle; Protein-Lysine 6-Oxidase; Basic Helix-Loop-Helix Transcription Factors; Humans; Female; Mixed Function Oxygenases; Cell Line, Tumor; Placental Lactogen