PMID- 11853549
OWN - NLM
STAT- MEDLINE
DCOM- 20020403
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 362
IP  - Pt 2
DP  - 2002 Mar 1
TI  - Transcriptional regulation of the human manganese superoxide dismutase gene: the 
      role of specificity protein 1 (Sp1) and activating protein-2 (AP-2).
PG  - 401-12
AB  - Manganese superoxide dismutase (MnSOD) plays an important role in regulating 
      cellular redox conditions. Expression of MnSOD has been shown to protect against 
      damage by oxidative stress and to suppress the malignant phenotype of human 
      cancer cells. We have previously cloned the human MnSOD (SOD2) gene and analysed 
      its 5' proximal promoter, which has been characterized by a lack of a TATA or 
      CAAT box and the presence of multiple GC boxes. To define further the molecular 
      mechanisms for the regulation of MnSOD expression, multiple transcription 
      factor-binding motifs containing overlapping specificity protein 1 (Sp1)- and 
      activator protein (AP)-2-binding sites were identified by DNase I footprinting 
      analysis. Functional studies in three cell lines with different levels of Sp1 and 
      AP-2 proteins suggested that the cellular levels of these proteins may 
      differentially regulate transcription via GC-binding motifs in the human SOD2 
      promoter. Co-transfection of an Sp1 expression vector resulted in an increase in 
      the transcription of the promoter-driven reporter gene. In contrast, 
      co-transfection of the AP-2 expression vector caused a decrease in transcription. 
      Direct mutagenesis analysis of Sp1- and AP-2-binding sites showed that Sp1 is 
      essential for transcription of the human SOD2 gene, whereas AP-2 plays a negative 
      role in the transcription. Immunoprecipitation of Sp1 and AP-2 proteins 
      demonstrated that Sp1 interacts with AP-2 in vivo. Two-hybrid analysis revealed 
      that interaction between Sp1 and AP-2 plays both a positive and negative role in 
      the transcription of the reporter gene in vivo. Taken together, our data indicate 
      that AP-2 down-regulates transcription of the human SOD2 gene via its interaction 
      with Sp1 within the promoter region. These findings, coupled with our previous 
      observation that several cancer cell lines have mutations in the promoter region 
      of the human MnSOD gene, which lead to an increase in an AP-2-binding site and a 
      decrease in the promoter activity, signal the importance of understanding the 
      promoter structure and the regulation of the human SOD2 gene by Sp1 and AP-2.
FAU - Xu, Yong
AU  - Xu Y
AD  - Graduate Center for Toxicology, University of Kentucky, 361 Health Sciences 
      Research Building, Lexington KY 40536, USA.
FAU - Porntadavity, Sureerut
AU  - Porntadavity S
FAU - St Clair, Daret K
AU  - St Clair DK
LA  - eng
GR  - CA 49797/CA/NCI NIH HHS/United States
GR  - CA 59835/CA/NCI NIH HHS/United States
GR  - CA 73599/CA/NCI NIH HHS/United States
GR  - HL 03544/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (KLF12 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (Transcription Factors)
RN  - 5Z93L87A1R (Guanine)
RN  - 8J337D1HZY (Cytosine)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - Carcinoma, Hepatocellular
MH  - Cell Line, Transformed
MH  - Cloning, Molecular
MH  - Cytosine
MH  - DNA Primers
MH  - DNA-Binding Proteins/*metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Genes, Reporter
MH  - Guanine
MH  - HeLa Cells
MH  - Humans
MH  - Kruppel-Like Transcription Factors
MH  - Liver Neoplasms
MH  - Lung
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Plasmids
MH  - Promoter Regions, Genetic
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Deletion
MH  - Superoxide Dismutase/chemistry/*genetics
MH  - Transcription Factor AP-2
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Tumor Cells, Cultured
PMC - PMC1222401
EDAT- 2002/02/21 10:00
MHDA- 2002/04/04 10:01
PMCR- 2002/09/01
CRDT- 2002/02/21 10:00
PHST- 2002/02/21 10:00 [pubmed]
PHST- 2002/04/04 10:01 [medline]
PHST- 2002/02/21 10:00 [entrez]
PHST- 2002/09/01 00:00 [pmc-release]
AID - 10.1042/0264-6021:3620401 [doi]
PST - ppublish
SO  - Biochem J. 2002 Mar 1;362(Pt 2):401-12. doi: 10.1042/0264-6021:3620401.