کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1953402 | 1057270 | 2006 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential responses of two degradation domains of HIF-1α to hypoxia and iron deficiency
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
HIF-1α is a transcription factor involved in the cellular adaptation to either hypoxia or iron deficiency. In the presence of oxygen and iron, proline residues in two degradation domains are modified by HIF-1-prolyl hydroxylases (PHDs), resulting in ubiquitination and degradation of HIF-1α. Since both molecular oxygen and iron are elements required for this hydroxylation process, HIF-1α might be unmodified and stable in conditions lacking oxygen or iron. If so, two degradation domains may respond to hypoxia and iron-depletion in the same way. In this study, however, we found two degradation domains to differentially regulate the stability of HIF-1α. The C-terminal domain responded to both hypoxia and iron-depletion, but the N-terminal domain to only iron-depletion. The deletion or point-mutation of the C-terminal domain blunted the hypoxic induction of HIF-1α. However, PHD-silencing siRNAs revealed that two degradation domains were not regulated by different types of PHDs. Both domains were regulated mainly by PHD2. The further mutational analysis demonstrated that the ARD1-acetylated motif near the C-terminal degradation domain (CDD) modulates the oxygen-dependent regulation of HIF-1α. The oxygen-dependent HIF-1α regulation requiring both proline hydroxylation and lysine acetylation may be more complicated than the iron-dependent regulation requiring only proline hydroxylation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 88, Issue 2, February 2006, Pages 163-169
Journal: Biochimie - Volume 88, Issue 2, February 2006, Pages 163-169
نویسندگان
Kyoung-Hwa Lee, Eunjoo Choi, Yang-Sook Chun, Myung-Suk Kim, Jong-Wan Park,