Crif1 is a novel transcriptional coactivator of STAT3

Min Chul Kwon, Bon Kyoung Koo, Jin Sook Moon, Yoon Young Kim, Ki Cheol Park, Nam Shik Kim, Mi Yi Kwon, Myung Phil Kong, Ki Jun Yoon, Sun Kyoung Im, Jaewang Ghim, Yong Mahn Han, Sung Key Jang, Minho Shong, Young Yun Kong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)642-653
Number of pages12
JournalEMBO Journal
Volume27
Issue number4
DOIs
StatePublished - Feb 20 2008

Keywords

  • Crif1
  • Embryogenesis
  • STAT3
  • Transcriptional coactivator
  • Tumorigenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Crif1 is a novel transcriptional coactivator of STAT3'. Together they form a unique fingerprint.

  • Cite this

    Kwon, M. C., Koo, B. K., Moon, J. S., Kim, Y. Y., Park, K. C., Kim, N. S., Kwon, M. Y., Kong, M. P., Yoon, K. J., Im, S. K., Ghim, J., Han, Y. M., Jang, S. K., Shong, M., & Kong, Y. Y. (2008). Crif1 is a novel transcriptional coactivator of STAT3. EMBO Journal, 27(4), 642-653. https://doi.org/10.1038/sj.emboj.7601986