Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN)

Won Il Choi, Bu Nam Jeon, Hyejin Park, Jung Yoon Yoo, Yeon Sook Kim, Dong In Koh, Myung Hwa Kim, Yu Ri Kim, Choong Eun Lee, Kyung Sup Kim, Timothy F. Osborne, Man Wook Hur

Research output: Contribution to journalArticle

Abstract

FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-à-brac, tramtrack, and broad complex and pox virus zinc finger) domain family. Recent evidence suggested that FBI-1 might be involved in adipogenic gene expression. Coincidentally, expression of FBI-1 and fatty-acid synthase (FASN) genes are often increased in cancer and immortalized cells. Both FBI-1 and FASN are important in cancer cell proliferation. SREBP-1 is a major regulator of many adipogenic genes, and FBI-1 and SREBP-1 (sterol-responsive element (SRE)-binding protein 1) interact with each other directly via their DNA binding domains. FBI-1 enhanced the transcriptional activation of SREBP-1 on responsive promoters, pGL2-6x(SRE)-Luc and FASN gene. FBI-1 and SREBP-1 synergistically activate transcription of the FASN gene by acting on the proximal GC-box and SRE/E-box. FBI-1, Sp1, and SREBP-1 can bind to all three SRE, GC-box, and SRE/E-box. Binding competition among the three transcription factors on the GC-box and SRE/E-box appears important in the transcription regulation. FBI-1 is apparently changing the binding pattern of Sp1 and SREBP-1 on the two elements in the presence of induced SREBP-1 and drives more Sp1 binding to the proximal promoter with less of an effect on SREBP-1 binding. The changes induced by FBI-1 appear critical in the synergistic transcription activation. The molecular mechanism revealed provides insight into how proto-oncogene FBI-1 may attack the cellular regulatory mechanism of FASN gene expression to provide more phospholipid membrane components needed for rapid cancer cell proliferation.

Original languageEnglish (US)
Pages (from-to)29341-29354
Number of pages14
JournalJournal of Biological Chemistry
Volume283
Issue number43
DOIs
StatePublished - Oct 24 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Choi, W. I., Jeon, B. N., Park, H., Yoo, J. Y., Kim, Y. S., Koh, D. I., Kim, M. H., Kim, Y. R., Lee, C. E., Kim, K. S., Osborne, T. F., & Hur, M. W. (2008). Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN). Journal of Biological Chemistry, 283(43), 29341-29354. https://doi.org/10.1074/jbc.M802477200