PMID- 25687434
OWN - NLM
STAT- MEDLINE
DCOM- 20160223
LR  - 20181113
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 240
IP  - 11
DP  - 2015 Nov
TI  - Featured Article: Hypoxia-inducible factor-1alpha dependent nuclear entry of factor 
      inhibiting HIF-1.
PG  - 1446-51
LID - 10.1177/1535370215570821 [doi]
AB  - The regulation of hypoxia-inducible factor-1 (HIF-1) transcriptional activity in 
      the nucleus is related to factor inhibiting HIF-1 (FIH-1). FIH-1 hydrolyzes 
      asparagine at the C-terminal of HIF-1alpha, preventing the interaction between HIF-1alpha 
      and its associated cofactors, and leading to suppressed activation of HIF-1. 
      FIH-1 is a cytosolic protein and its entry to the nucleus has to be coordinated 
      with HIF-1alpha. The present study was undertaken to examine the correlation between 
      HIF-1alpha and FIH-1 in their nuclear entry. Human umbilical vein endothelial cells 
      were treated with dimethyloxalylglycine at a final concentration of 100 microM for 
      4 h, resulting in an accumulation of HIF-1alpha and an increase of FIH-1 in the 
      nucleus as determined by Western blot analysis. Pretreatment of the cells with 
      copper (Cu) chelator tetraethylenepentamine at 50 microM in cultures for 24 h reduced 
      both HIF-1alpha protein levels and the HIF-1alpha entry to the nucleus, along with 
      decreased FIH-1 protein levels in the nucleus but no changes in the total FIH-1 
      protein levels in the cells. These effects were prevented by simultaneous 
      addition of 50 microM CuSO4 with tetraethylenepentamine. Gene-silencing of HIF-1alpha 
      significantly inhibited FIH-1 entry to the nucleus, but did not affect the total 
      protein levels of FIH-1 in the cells. This work demonstrates that the nuclear 
      entry of FIH-1 depends on HIF-1alpha. Cu deficiency caused a decrease of HIF-1alpha, 
      leading to suppression of FIH-1 entry to the nucleus.
CI  - (c) 2015 by the Society for Experimental Biology and Medicine.
FAU - Liang, Ke
AU  - Liang K
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, Sichuan 610041, China.
FAU - Ding, Xue-Qin
AU  - Ding XQ
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, Sichuan 610041, China.
FAU - Lin, Chen
AU  - Lin C
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, Sichuan 610041, China.
FAU - Kang, Y James
AU  - Kang YJ
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, Sichuan 610041, China yjkang01@louisville.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150216
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Amino Acids, Dicarboxylic)
RN  - 0 (Chelating Agents)
RN  - 0 (Ethylenediamines)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 7006-34-0 (Asparagine)
RN  - 789U1901C5 (Copper)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.11.- (HIF1AN protein, human)
RN  - LRX7AJ16DT (Copper Sulfate)
RN  - VVW38EB8YS (oxalylglycine)
RN  - YZD1C9KQ28 (tetraethylenepentamine)
SB  - IM
MH  - *Active Transport, Cell Nucleus
MH  - Amino Acids, Dicarboxylic/chemistry
MH  - Asparagine/chemistry
MH  - Cell Nucleus/metabolism
MH  - Chelating Agents/chemistry
MH  - Copper/chemistry
MH  - Copper Sulfate/chemistry
MH  - Cytoplasm/metabolism
MH  - Cytosol/metabolism
MH  - Ethylenediamines/chemistry
MH  - Gene Silencing
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Hydrolysis
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Mixed Function Oxygenases/*metabolism
MH  - Protein Structure, Tertiary
MH  - RNA, Small Interfering/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Transcription, Genetic
PMC - PMC4935306
OTO - NOTNLM
OT  - Copper
OT  - FIH-1
OT  - HIF-1
OT  - gene silencing
OT  - nuclear entry
OT  - tetraethylenepentamine
EDAT- 2015/02/18 06:00
MHDA- 2016/02/26 06:00
PMCR- 2016/05/01
CRDT- 2015/02/18 06:00
PHST- 2014/07/25 00:00 [received]
PHST- 2014/12/18 00:00 [accepted]
PHST- 2015/02/18 06:00 [entrez]
PHST- 2015/02/18 06:00 [pubmed]
PHST- 2016/02/26 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 1535370215570821 [pii]
AID - 10.1177_1535370215570821 [pii]
AID - 10.1177/1535370215570821 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2015 Nov;240(11):1446-51. doi: 10.1177/1535370215570821. 
      Epub 2015 Feb 16.