PMID- 17937768
OWN - NLM
STAT- MEDLINE
DCOM- 20080117
LR  - 20131121
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 274
IP  - 21
DP  - 2007 Nov
TI  - Transcription of mammalian cytochrome c oxidase subunit IV-2 is controlled by a 
      novel conserved oxygen responsive element.
PG  - 5737-48
AB  - Subunit 4 of cytochrome c oxidase (CcO) is a nuclear-encoded regulatory subunit 
      of the terminal complex of the mitochondrial electron transport chain. We have 
      recently discovered an isoform of CcO 4 (CcO4-2) which is specific to lung and 
      trachea, and is induced after birth. The role of CcO as the major cellular oxygen 
      consumer, and the lung-specific expression of CcO4-2, led us to investigate 
      CcO4-2 gene regulation. We cloned the CcO4-2 promoter regions of cow, rat and 
      mouse and compared them with the human promoter. Promoter activity is localized 
      within a 118-bp proximal region of the human promoter and is stimulated by 
      hypoxia, reaching a maximum (threefold) under 4% oxygen compared with normoxia. 
      CcO4-2 oxygen responsiveness was assigned by mutagenesis to a novel promoter 
      element (5'-GGACGTTCCCACG-3') that lies within a 24-bp region that is 79% 
      conserved in all four species. This element is able to bind protein, and 
      competition experiments revealed that, within the element, the four core bases 
      5'-TCNCA-3' are obligatory for transcription factor binding. CcO isolated from 
      lung showed a 2.5-fold increased maximal turnover compared with liver CcO. We 
      propose that CcO4-2 expression in highly oxygenated lung and trachea protects 
      these tissues from oxidative damage by accelerating the last step in the electron 
      transport chain, leading to a decrease in available electrons for free radical 
      formation.
FAU - Huttemann, Maik
AU  - Huttemann M
AD  - Molecular Medicine and Genetics, Wayne State University School of Medicine, 
      Detroit, MI 48201, USA. mhuttema@med.wayne.edu
FAU - Lee, Icksoo
AU  - Lee I
FAU - Liu, Jenney
AU  - Liu J
FAU - Grossman, Lawrence I
AU  - Grossman LI
LA  - eng
SI  - GENBANK/AY219183
GR  - GM48517/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071012
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Electron Transport Complex IV/*genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Lung/metabolism
MH  - Mammals
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oxygen/*metabolism
MH  - Phylogeny
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - *Response Elements
MH  - *Transcription, Genetic
MH  - Transfection
EDAT- 2007/10/17 09:00
MHDA- 2008/01/18 09:00
CRDT- 2007/10/17 09:00
PHST- 2007/10/17 09:00 [pubmed]
PHST- 2008/01/18 09:00 [medline]
PHST- 2007/10/17 09:00 [entrez]
AID - EJB6093 [pii]
AID - 10.1111/j.1742-4658.2007.06093.x [doi]
PST - ppublish
SO  - FEBS J. 2007 Nov;274(21):5737-48. doi: 10.1111/j.1742-4658.2007.06093.x. Epub 
      2007 Oct 12.