title: Crif1 is a novel transcriptional coactivator of STAT3.
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.
authors.affiliation: Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Min-chul
authors.initials: MC
authors.lastname: Kwon
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Moon
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.forename: Nam-Shik
authors.initials: NS
authors.lastname: Kim
authors.forename: Mi Yi
authors.initials: MY
authors.lastname: Kwon
authors.forename: Myung-Phil
authors.initials: MP
authors.lastname: Kong
authors.forename: Ki-Jun
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Sun-Kyoung
authors.initials: SK
authors.lastname: Im
authors.forename: Jaewang
authors.initials: J
authors.lastname: Ghim
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; C527307:Crif1 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004247:DNA