Biochemical Characterization of Human Prolyl Hydroxylase Domain Protein 2 Variants Associated with Erythrocytosis

Biochemistry ◽  
2008 ◽  
Vol 47 (43) ◽  
pp. 11165-11167 ◽  
Author(s):  
Melissa B. Pappalardi ◽  
John D. Martin ◽  
Yong Jiang ◽  
Matthew C. Burns ◽  
Huizhen Zhao ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Prolyl Hydroxylase ◽  
Domain Protein ◽  
Prolyl Hydroxylase Domain

Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites

2011 ◽  
Vol 436 (2) ◽  
pp. 363-369 ◽  
Author(s):  
Melissa B. Pappalardi ◽  
Dean E. McNulty ◽  
John D. Martin ◽  
Kelly E. Fisher ◽  
Yong Jiang ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Transactivation Domain ◽  
Prolyl Hydroxylases ◽  
Proline Residue ◽  
Protein Substrates ◽  
Steady State Kinetic ◽  
Asparaginyl Hydroxylase

The HIF (hypoxia-inducible factor) plays a central regulatory role in oxygen homoeostasis. HIF proteins are regulated by three Fe(II)- and α-KG (α-ketoglutarate)-dependent prolyl hydroxylase enzymes [PHD (prolyl hydroxylase domain) isoenzymes 1–3 or PHD1, PHD2 and PHD3] and one asparaginyl hydroxylase [FIH (factor inhibiting HIF)]. The prolyl hydroxylases control the abundance of HIF through oxygen-dependent hydroxylation of specific proline residues in HIF proteins, triggering subsequent ubiquitination and proteasomal degradation. FIH inhibits the HIF transcription activation through asparagine hydroxylation. Understanding the precise roles and regulation of these four Fe(II)- and α-KG-dependent hydroxylases is of great importance. In the present paper, we report the biochemical characterization of the first HIF protein substrates that contain the CODDD (C-terminal oxygen-dependent degradation domain), the NODDD (N-terminal oxygen-dependent degradation domain) and the CAD (C-terminal transactivation domain). Using LC-MS/MS (liquid chromatography–tandem MS) detection, we show that all three PHD isoenzymes have a strong preference for hydroxylation of the CODDD proline residue over the NODDD proline residue and the preference is observed for both HIF1α and HIF2α protein substrates. In addition, steady-state kinetic analyses show differential substrate selectivity for HIF and α-KG in reference to the three PHD isoforms and FIH.

scholarly journals Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption

2014 ◽  
Vol 126 (9) ◽  
pp. 671-678 ◽  
Author(s):  
Aya Watanabe ◽  
Toshihiro Ichiki ◽  
Chikahiro Sankoda ◽  
Yusuke Takahara ◽  
Jiro Ikeda ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cobalt Chloride ◽  
Prolyl Hydroxylase ◽  
Abdominal Aneurysm ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Domain Protein ◽  
Prolyl Hydroxylase Domain

Inhibition of prolyl hydroxylase domain protein by cobalt chloride suppressed calcium chloride-induced abdominal aneurysm formation in mice.

miR-21 contributes to renal protection by targeting prolyl hydroxylase domain protein 2 in delayed ischaemic preconditioning

Nephrology ◽  
2017 ◽  
Vol 22 (5) ◽  
pp. 366-373 ◽  
Author(s):  
Xiaoyan Jiao ◽  
Xialian Xu ◽  
Yi Fang ◽  
Hui Zhang ◽  
Mingyu Liang ◽  
...  
Keyword(s):  
Prolyl Hydroxylase ◽  
Ischaemic Preconditioning ◽  
Renal Protection ◽  
Domain Protein ◽  
Prolyl Hydroxylase Domain

scholarly journals The Role of Prolyl Hydroxylase Domain Protein (PHD) during Rosiglitazone-induced Adipocyte Differentiation

2013 ◽  
Vol 289 (5) ◽  
pp. 2755-2764 ◽  
Author(s):  
Juyoung Kim ◽  
Hyun Jeong Kwak ◽  
Ji-Young Cha ◽  
Yun-Seung Jeong ◽  
Sang Dahl Rhee ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Prolyl Hydroxylase ◽  
Domain Protein ◽  
Prolyl Hydroxylase Domain
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