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

Authors
 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 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.283(43) : 29341-29354, 2008 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2008
MeSH
Animals ; Cell Proliferation ; DNA-Binding Proteins/metabolism* ; Fatty Acid Synthases/biosynthesis* ; Fatty Acid Synthases/genetics* ; Gene Expression Regulation, Enzymologic* ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Proto-Oncogene Proteins/metabolism ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Transcription Factors/metabolism* ; Transcription, Genetic*
Keywords
Animals ; Cell Proliferation ; DNA-Binding Proteins/metabolism* ; Fatty Acid Synthases/biosynthesis* ; Fatty Acid Synthases/genetics* ; Gene Expression Regulation, Enzymologic* ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Proto-Oncogene Proteins/metabolism ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Transcription Factors/metabolism* ; Transcription, Genetic*
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.
Files in This Item:
T200800686.pdf Download
DOI
10.1074/jbc.M802477200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Myung Hwa(김명화)
Kim, Yeon Sook(김연숙)
Kim, Yu Ri(김유리)
Park, Hye Jin(박혜진)
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Jeon, Bu Nam(전부남)
Choi, Won Il(최원일)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106936
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