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Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.
Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG Jr, Zhang Q. Zheng X, et al. Among authors: brenner mc. Genes Dev. 2014 Jul 1;28(13):1429-44. doi: 10.1101/gad.242131.114. Genes Dev. 2014. PMID: 24990963 Free PMC article.
Many amino acid substitutions in a hypoxia-inducible transcription factor (HIF)-1alpha-like peptide cause only minor changes in its hydroxylation by the HIF prolyl 4-hydroxylases: substitution of 3,4-dehydroproline or azetidine-2-carboxylic acid for the proline leads to a high rate of uncoupled 2-oxoglutarate decarboxylation.
Li D, Hirsilä M, Koivunen P, Brenner MC, Xu L, Yang C, Kivirikko KI, Myllyharju J. Li D, et al. Among authors: brenner mc. J Biol Chem. 2004 Dec 31;279(53):55051-9. doi: 10.1074/jbc.M410287200. Epub 2004 Oct 12. J Biol Chem. 2004. PMID: 15485863 Free article.
Nonclinical Characterization of the Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat, a Novel Treatment of Anemia of Chronic Kidney Disease.
Del Balzo U, Signore PE, Walkinshaw G, Seeley TW, Brenner MC, Wang Q, Guo G, Arend MP, Flippin LA, Chow FA, Gervasi DC, Kjaergaard CH, Langsetmo I, Guenzler V, Liu DY, Klaus SJ, Lin A, Neff TB. Del Balzo U, et al. Among authors: brenner mc. J Pharmacol Exp Ther. 2020 Aug;374(2):342-353. doi: 10.1124/jpet.120.265181. Epub 2020 Jun 2. J Pharmacol Exp Ther. 2020. PMID: 32487538
19 results