Different roles of Sp family members in HIV-1 Tat-mediated manganese superoxide dismutase suppression in hepatocellular carcinoma cells
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
DNA and cell biology - 24(2005), 5 vom: 11. Mai, Seite 299-310 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Porntadavity, Sureerut [VerfasserIn] |
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| Anmerkungen: |
Date Completed 27.05.2005 Date Revised 21.11.2008 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM155167758 |
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| 100 | 1 | |a Porntadavity, Sureerut |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Different roles of Sp family members in HIV-1 Tat-mediated manganese superoxide dismutase suppression in hepatocellular carcinoma cells |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 27.05.2005 | ||
| 500 | |a Date Revised 21.11.2008 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Gene Products, tat |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Sp1 Transcription Factor |2 NLM | |
| 650 | 7 | |a tat Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 650 | 7 | |a Luciferases |2 NLM | |
| 650 | 7 | |a EC 1.13.12.- |2 NLM | |
| 650 | 7 | |a Superoxide Dismutase |2 NLM | |
| 650 | 7 | |a EC 1.15.1.1 |2 NLM | |
| 650 | 7 | |a beta-Galactosidase |2 NLM | |
| 650 | 7 | |a EC 3.2.1.23 |2 NLM | |
| 700 | 1 | |a Nath, Avindra |e verfasserin |4 aut | |
| 700 | 1 | |a Prachayasittikul, Virapong |e verfasserin |4 aut | |
| 700 | 1 | |a Cota-Gomez, Adela |e verfasserin |4 aut | |
| 700 | 1 | |a Flores, Sonia C |e verfasserin |4 aut | |
| 700 | 1 | |a St Clair, Daret K |e verfasserin |4 aut | |
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