Journal article
A Family of AP-2 Proteins Down-regulate Manganese Superoxide Dismutase Expression
The Journal of biological chemistry, Vol.276(17), pp.14407-14413
04/2001
DOI: 10.1074/jbc.M009708200
PMID: 11278550
Abstract
Manganese superoxide dismutase (Mn-SOD) is a primary antioxidant enzyme whose expression is essential for life in oxygen. Mn-SOD has tumor suppressor activity in a wide variety of tumors and transformed cell systems. Our initial observations revealed that Mn-SOD expression was inversely correlated with expression of AP-2 transcription factors in normal human fibroblasts and their SV-40 transformed counterparts. Thus we hypothesized that AP-2 may down-regulate Mn-SOD expression. To examine the functional role of AP-2 on Mn-SOD promoter transactivation we cotransfected AP-2-deficient HepG2 cells with a human Mn-SOD promoter-reporter construct and expression vectors encoding each of the three known AP-2 family members. Our results indicated that AP-2 could significantly repress Mn-SOD promoter activity, and that this repression was both Mn-SOD promoter and AP-2-specific. The three AP-2 proteins appeared to play distinct roles in Mn-SOD gene regulation. Moreover, although all three AP-2 proteins could repress the Mn-SOD promoter, AP-2α and AP-2γ were more active in this regard than AP-2β. Transcriptional repression by AP-2 was not a general effect in this system, because another AP-2-responsive gene, c-erbB-3, was transactivated by AP-2. Repression of Mn-SOD by AP-2 was dependent on DNA binding, and expression of AP-2B, a dominant negative incapable of DNA binding, relieved the repression on Mn-SOD promoter and reactivated Mn-SOD expression in the AP-2 abundant SV40-transformed fibroblast cell line MRC-5VA. These results indicate that AP-2-mediated transcriptional repression contributes to the constitutively low expression of Mn-SOD in SV40-transfromed fibroblasts and suggest a mechanism for Mn-SOD down-regulation in cancer.
Details
- Title: Subtitle
- A Family of AP-2 Proteins Down-regulate Manganese Superoxide Dismutase Expression
- Creators
- Chun-Hong ZhuYuanhui HuangLarry W OberleyFrederick E Domann
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.276(17), pp.14407-14413
- DOI
- 10.1074/jbc.M009708200
- PMID
- 11278550
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 04/2001
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047672202771
Metrics
22 Record Views