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  • 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

Correspondence to:

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

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