PMID- 18518878
OWN - NLM
STAT- MEDLINE
DCOM- 20090619
LR  - 20201209
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 35
IP  - 10
DP  - 2008 Oct
TI  - Identification of a novel repressor element in the cyclo-oxygenase-2 promoter and 
      its nuclear binding protein.
PG  - 1204-8
LID - 10.1111/j.1440-1681.2008.04980.x [doi]
AB  - Cyclo-oxygenase-2 (COX-2) has important functions in many diseases. Although its 
      transcriptional regulation has been investigated in considerable detail, some 
      important elements remain unknown. The aim of the present study was to 
      demonstrate the existence of a novel repressor element in the mouse COX-2 
      promoter and characterize some of its binding proteins. In order to identify the 
      repressor element, the activity of the mouse COX-2 promoter was investigated in 
      the pancreatic beta-cell line RINm5F using a series of deletion and mutant 
      constructs. The ability of nuclear proteins to bind to this repressor element was 
      then determined by an electrophoretic mobility shift assay and the proteins 
      binding to this repressor element were purified and identified by mass 
      spectrometry. One of the nuclear proteins identified was overexpressed to examine 
      its inhibitory effect on COX-2 promoter activity. We found a novel repressor 
      element located from nucleotides -655 to -632 of the mouse COX-2 promoter region. 
      Some proteins from RINm5F cell nuclear extracts bound to this element, one of 
      which was identified as non-POU-domain-containing, octamer-binding protein 
      (NonO). Overexpression of NonO significantly inhibited wild-type COX-2 promoter 
      activity, but had no effect when the repressor element was mutated. In 
      conclusion, we have demonstrated that a regulatory 'spot' is present in the COX-2 
      promoter. This provides additional data on COX-2 gene regulation and may provide 
      an insight into the clinical treatment of diseases where COX-2 is highly 
      expressed.
FAU - Yang, Xiaomin
AU  - Yang X
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical 
      University, Nanjing, China.
FAU - Lin, Ling
AU  - Lin L
FAU - Zhang, Xiongfei
AU  - Zhang X
FAU - Ji, Yong
AU  - Ji Y
FAU - Lv, Jinghuan
AU  - Lv J
FAU - Zhu, Yunxia
AU  - Zhu Y
FAU - Yin, Yongmei
AU  - Yin Y
FAU - Sun, Yujie
AU  - Sun Y
FAU - Han, Xiao
AU  - Han X
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080601
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nono protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 1.13.12.5 (Luciferases, Renilla)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 2/*genetics/*metabolism
MH  - DNA-Binding Proteins/biosynthesis/*genetics/metabolism/physiology
MH  - Down-Regulation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Insulin-Secreting Cells/enzymology/metabolism/pathology
MH  - Luciferases, Renilla
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*genetics/*metabolism
MH  - Promoter Regions, Genetic/*physiology
MH  - Protein Binding/physiology
MH  - RNA-Binding Proteins
MH  - Repressor Proteins/*genetics/*metabolism
EDAT- 2008/06/04 09:00
MHDA- 2009/06/20 09:00
CRDT- 2008/06/04 09:00
PHST- 2008/06/04 09:00 [pubmed]
PHST- 2009/06/20 09:00 [medline]
PHST- 2008/06/04 09:00 [entrez]
AID - CEP4980 [pii]
AID - 10.1111/j.1440-1681.2008.04980.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1204-8. doi: 
      10.1111/j.1440-1681.2008.04980.x. Epub 2008 Jun 1.