Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-5-4
pubmed:abstractText
The expression of manganese superoxide dismutase (MnSOD) is regulated by agents associated with cancer development. It has been shown that infection with the human immunodeficiency virus type 1 (HIV-1) is associated with the development of liver cancer and that the transactivating transcriptional factor (Tat) of human HIV-1 reduces the expression of MnSOD in several cell types. However, the role of Tat in the expression of MnSOD in hepatocellular carcinoma is unknown. Furthermore, the precise mechanisms whereby Tat suppresses MnSOD expression in hepatocellular carcinoma cells remain unclear. In this report, we build on our original observations that Tat changes the distribution of Sp family members on the MnSOD promoter, which accounts for Tat-dependent changes in basal expression. In hepatic cells, Tat expression upregulates Sp1/Sp3, which play different roles in regulating MnSOD transcription. While overexpression of Sp1 stimulates, overexpression of Sp3 represses transcriptional activity. The transcription repression effect of Sp3 is not due to Sp3 competing for the binding site with Sp1 because only the full-length Sp3 but not the truncated Sp3 suppresses MnSOD promoter activity. These findings suggest a novel mechanism by which Tat modulates the repression of the MnSOD gene and establish a link between HIV infection and liver cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
299-310
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15869407-Blotting, Western, pubmed-meshheading:15869407-Carcinoma, Hepatocellular, pubmed-meshheading:15869407-Cell Line, Transformed, pubmed-meshheading:15869407-Cell Line, Tumor, pubmed-meshheading:15869407-Gene Expression Regulation, Enzymologic, pubmed-meshheading:15869407-Gene Products, tat, pubmed-meshheading:15869407-Genes, Reporter, pubmed-meshheading:15869407-HIV-1, pubmed-meshheading:15869407-Humans, pubmed-meshheading:15869407-Liver Neoplasms, pubmed-meshheading:15869407-Luciferases, pubmed-meshheading:15869407-Plasmids, pubmed-meshheading:15869407-Promoter Regions, Genetic, pubmed-meshheading:15869407-RNA, Messenger, pubmed-meshheading:15869407-Sp1 Transcription Factor, pubmed-meshheading:15869407-Superoxide Dismutase, pubmed-meshheading:15869407-Transcription, Genetic, pubmed-meshheading:15869407-Transfection, pubmed-meshheading:15869407-beta-Galactosidase, pubmed-meshheading:15869407-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2005
pubmed:articleTitle
Different roles of Sp family members in HIV-1 Tat-mediated manganese superoxide dismutase suppression in hepatocellular carcinoma cells.
pubmed:affiliation
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.