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Article
Subject Categories: Signal Transduction | Chromatin & Transcription
The EMBO Journal (2008) 27, 642–653, doi:10.1038/sj.emboj.7601986
Published online 17 January 2008
Crif1 is a novel transcriptional coactivator of STAT3
Min-chul Kwon1, Bon-Kyoung Koo1, Jin-Sook Moon1, Yoon-Young Kim1, Ki Cheol Park2, Nam-Shik Kim1, Mi Yi Kwon1, Myung-Phil Kong1, Ki-Jun Yoon1, Sun-Kyoung Im1, Jaewang Ghim1, Yong-Mahn Han3, Sung Key Jang1, Minho Shong2 and Young-Yun Kong1
1 Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, South Korea
2 Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea
3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, South Korea

To whom correspondence should be addressed
Young-Yun Kong, Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Kyungbuk, Pohang 790-784, South Korea. Tel.: +82 54 279 2287; Fax: +82 54 279 2199; E-mail: ykong@postech.ac.kr

Received 28 August 2007; Accepted 2 January 2008; Published online 17 January 2008.
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor that performs a broad spectrum of biological functions in response to various stimuli. However, no specific coactivator that regulates the transcriptional activity of STAT3 has been identified. Here we report that CR6-interacting factor 1 (Crif1) is a specific transcriptional coactivator of STAT3, but not of STAT1 or STAT5a. Crif1 interacts with STAT3 and positively regulates its transcriptional activity. Crif1-/- embryos were lethal around embryonic day 6.5, and manifested developmental arrest accompanied with defective proliferation and massive apoptosis. The expression of STAT3 target genes was markedly reduced in a Crif1-/- blastocyst culture and in Oncostatin M-stimulated Crif1-deficient MEFs. Importantly, the key activities of constitutively active STAT3-C, such as transcription, DNA binding, and cellular transformation, were abolished in the Crif1-null MEFs, suggesting the essential role of Crif1 in the transcriptional activity of STAT3. Our results reveal that Crif1 is a novel and essential transcriptional coactivator of STAT3 that modulates its DNA binding ability, and shed light on the regulation of oncogenic STAT3.
Keywords: Crif1, embryogenesis, STAT3, transcriptional coactivator, tumorigenesis
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