Proto-oncogene FBI-1 (Pokemon) and SREBP-1 Synergistically Activate Transcription of Fatty-acid Synthase Gene (FASN)

被引:70
作者
Choi, Won-Il [1 ]
Jeon, Bu-Nam [1 ]
Park, Hyejin [1 ]
Yoo, Jung-Yoon [1 ]
Kim, Yeon-Sook [1 ]
Koh, Dong-In [1 ]
Kim, Myung-Hwa [1 ]
Kim, Yu-Ri [1 ]
Lee, Choong-Eun [2 ]
Kim, Kyung-Sup [1 ]
Osborne, Timothy F. [3 ]
Hur, Man-Wook [1 ]
机构
[1] Yonsei Univ, Sch Med, Dept Biochem & Mol Biol, Inst Genet Sci,Brain Korea Project Med Sci 21, Seoul 120752, South Korea
[2] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea
[3] Univ Calif Irvine, Sch Biol Sci, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
关键词
D O I
10.1074/jbc.M802477200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-a-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.
引用
收藏
页码:29341 / 29354
页数:14
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