Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 377, Issue 1, Pages 317-320Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.10.003
Keywords
DUSP6; MKP-3; MAPK; ERK2; ETS; Promoter; Chromatin immunoprecipitation; Transcriptional factor; Feedback; Pancreatic cancer
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japanese Society of Gastroenterology
- Pancreas Research Foundation of Japan
- Promoting the Establishment of Strategic Research Centers
- Promoting Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology (Japan)
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DUSP6/MKP-3 is a dual Specificity phosphatase exclusively specific to MAPK1/ERK2 for its substrate recognition and dephosphorylating activity. DUSP6 is demonstrated to play a negative regulatory role in MAPK1 in a feedback loop manner: however, the regulation mechanisms of its expression in human cells have been largely unknown. We Previously found that human pancreatic cancer cells frequently lost DUSP6 expression, which could induce Constitutively active MAPK1, and the loss was associated with hypermethylation of the CpG cluster region of intron I of DUSP6. In this study, we investigated the promoter activity of intron I of DUSP6 in human cells. We demonstrated that the intron indeed had promoter activity and this activity was associated with MAPK1 activity. Moreover, promoter activity depended on a consensus binding sequence of ETS transcription factors and ETS2 was specifically associated with the intron. Because ETS2 is a direct target of MAPK, these results indicate that intron 1 of DUSP6 plays a crucial role in transcriptional regulation of DUSP6 in a feedback loop manner responding to MAPK I via ETS2 in human cells. (C) 2008 Elsevier Inc. All rights reserved. l
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