Consequences of IkappaB alpha hydroxylation by the factor inhibiting HIF (FIH)

被引：20

作者：

Devries, Ingrid L. ^{[1
]}

Hampton-Smith, Rachel J. ^{[2
]}

Mulvihill, Melinda M. ^{[1
]}

Alverdi, Vera ^{[1
]}

Peet, Daniel J. ^{[2
]}

Komives, Elizabeth A. ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[2] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia

来源：

FEBS LETTERS | 2010年 / 584卷 / 23期

基金：

英国医学研究理事会;

关键词：

Hypoxia-inducible factor; Ankyrin repeat; Post-translational modification; Protein folding; Proteasome degradation; NF-KAPPA-B; ANKYRIN REPEAT DOMAIN; ASPARAGINYL HYDROXYLATION; BETA-HYDROXYLATION; PROTEINS; STABILITY; NOTCH;

D O I：

10.1016/j.febslet.2010.10.060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The factor inhibiting HIF-1 ( FIH-1) hydroxylates many ankyrin repeat-containing proteins including I kappa B alpha. It is widely speculated that hydroxylation of I kappa B alpha has functional consequences, but the effects of hydroxylation have not been demonstrated. We prepared hydroxylated I kappa B alpha and compared it to the unhydroxylated protein. Urea denaturation and amide H/D exchange experiments showed no change in the "foldedness" upon hydroxylation. Surface plasmon resonance measurements of binding to NF kappa B showed no difference in the NF kappa B binding kinetics or thermodynamics. Ubiquitin-independent proteasomal degradation experiments showed no difference in the half-life of the protein. Thus, it appears that hydroxylation of I kappa B alpha by FIH-1 is inconsequential, at least for the functions we could assay in vitro. Structured summary: MINT-8051494: NF-kappa-B p65 (uniprotkb:Q04207) physically interacts (MI: 0915) with NF-kappa-B p50 (uniprotkb:P25799) and I-kappa-B alpha (uniprotkb:O15111) by surface plasmon resonance (MI:0107) (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4725 / 4730

页数：6

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