This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, C.-C. Articles by Yang, P.-C. Search for Related Content PubMed Articles by Wang, C.-C. Articles by Yang, P.-C.

Synergistic Activation of the Tumor Suppressor, HLJ1, by the Transcription Factors YY1 and Activator Protein 1

¹ NTU Center for Genomic Medicine, National Taiwan University, Departments of ² Medical Research and ³ Internal Medicine, National Taiwan University Hospital, and ⁴ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China; ⁵ Department of Molecular Biotechnology, Da-Yeh University, Chang-hua, Taiwan, Republic of China, ⁶ Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, Taichung, Taiwan, Republic of China; and ⁷ Institute of Cancer Research, National Health Research Institute, Miaoli, Taiwan, Republic of China

Requests for reprints: Jeremy J.W. Chen, Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, No. 250, Kuo-Kuang Road, Taichung 40227, Taiwan, Republic of China. Phone: 886-4-22840896, ext. 125; Fax: 886-4-22853469; E-mail: jwchen{at}dragon.nchu.edu.tw.

HLJ1 is a novel tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. However, the mechanism of HLJ1 activation is currently unclear. Here, we identify an enhancer segment in the HLJ1 gene at –2,125 to –1,039 bp upstream of the transcription start site. A 50-bp element between –1,492 and –1,443 bp is the minimal enhancer segment, which includes the activator protein 1 (AP-1) site (–1,457 to –1,451 bp), an essential regulatory domain that binds the transcriptional factors FosB, JunB, and JunD. Chromatin immunoprecipitation assays confirm that these AP-1 family members bind to a specific site in the HLJ1 enhancer segment in vivo. Overexpression of either YY1 at promoter or AP-1 at enhancer results in a 3-fold increase in the transcriptional activity of HLJ1. We propose a novel mechanism whereby expression of the tumor suppressor, HLJ1, is up-regulated via enhancer AP-1 binding to promoter YY1 and the coactivator, p300, through DNA bending and multiprotein complex formation. The combined expression of AP-1 and YY1 enhances HLJ1 expression by more than five times and inhibits in vitro cancer cell invasion. Elucidation of the regulatory mechanism of HLJ1 expression may facilitate the development of personalized therapy by inhibiting cancer cell proliferation, angiogenesis, and metastasis. [Cancer Res 2007;67(10):4816–26]

This article has been cited by other articles:

				H.-W. Chen, J.-Y. Lee, J.-Y. Huang, C.-C. Wang, W.-J. Chen, S.-F. Su, C.-W. Huang, C.-C. Ho, J. J.W. Chen, M.-F. Tsai, et al. Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the Tumor Suppressor HLJ1 Cancer Res., September 15, 2008; 68(18): 7428 - 7438. [Abstract] [Full Text] [PDF]