PMID- 16155211
OWN - NLM
STAT- MEDLINE
DCOM- 20060119
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 68
IP  - 6
DP  - 2005 Dec
TI  - Inhibition of the catalytic activity of hypoxia-inducible 
      factor-1alpha-prolyl-hydroxylase 2 by a MYND-type zinc finger.
PG  - 1803-9
AB  - Hypoxia-induced gene expression is initiated when the hypoxia-inducible factor-1 
      (HIF-1) alpha subunit is stabilized in response to a lack of oxygen. An 
      HIF-1alpha-specific prolyl-hydroxylase (PHD) catalyzes hydroxylation of the 
      proline-564 and/or -402 residues of HIF-1alpha by an oxygen molecule. The 
      hydroxyproline then interacts with the ubiquitin E3 ligase von Hippel Lindau 
      protein and is degraded by an ubiquitin-dependent proteasome. PHD2 is the most 
      active of three PHD isoforms in hydroxylating HIF-1alpha. Structural analysis 
      showed that the N-terminal region of PHD2 contains a Myeloid translocation 
      protein 8, Nervy, and DEAF1 (MYND)-type zinc finger domain, whereas the catalytic 
      domain is located in its C-terminal region. We found that deletion of the MYND 
      domain increased the activity of both recombinant PHD2 protein and in 
      vitro-translated PHD2. The zinc chelator 
      N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine augmented the activity of 
      wild-type PHD2-F but not that of PHD2 lacking the MYND domain, confirming that 
      the zinc finger domain is inhibitory. Overexpression of PHD2 lacking the MYND 
      domain caused a greater reduction in the stability and function of HIF-1alpha 
      than did overexpression of wild-type PHD2, indicating that the MYND domain also 
      inhibits the catalytic activity of PHD2 in vivo.
FAU - Choi, Kyung-Ok
AU  - Choi KO
AD  - Department of Life Science, University of Seoul, 90 Cheonnong-dong, 
      Tongdaemun-gu, Seoul 130-743, Korea.
FAU - Lee, Taekyong
AU  - Lee T
FAU - Lee, Naery
AU  - Lee N
FAU - Kim, Ji-Hyun
AU  - Kim JH
FAU - Yang, Eun Gyeong
AU  - Yang EG
FAU - Yoon, Jung Min
AU  - Yoon JM
FAU - Kim, Jin Hwan
AU  - Kim JH
FAU - Lee, Tae Gyu
AU  - Lee TG
FAU - Park, Hyunsung
AU  - Park H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050909
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Immediate-Early Proteins)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Catalytic Domain
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Immediate-Early Proteins/*antagonists & inhibitors/chemistry/genetics
MH  - Mutagenesis
MH  - Oxygen/pharmacology
MH  - Procollagen-Proline Dioxygenase/*antagonists & inhibitors/chemistry/genetics
MH  - Protein Structure, Tertiary
MH  - Sequence Deletion
MH  - Transfection
MH  - Zinc Fingers/*physiology
EDAT- 2005/09/13 09:00
MHDA- 2006/01/20 09:00
CRDT- 2005/09/13 09:00
PHST- 2005/09/13 09:00 [pubmed]
PHST- 2006/01/20 09:00 [medline]
PHST- 2005/09/13 09:00 [entrez]
AID - mol.105.015271 [pii]
AID - 10.1124/mol.105.015271 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2005 Dec;68(6):1803-9. doi: 10.1124/mol.105.015271. Epub 2005 Sep 
      9.