Crif1 is a novel transcriptional coactivator of STAT3.
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.
Kwon
Min-chul
MC
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
Koo
Bon-Kyoung
BK
Moon
Jin-Sook
JS
Kim
Yoon-Young
YY
Park
Ki Cheol
KC
Kim
Nam-Shik
NS
Kwon
Mi Yi
MY
Kong
Myung-Phil
MP
Yoon
Ki-Jun
KJ
Im
Sun-Kyoung
SK
Ghim
Jaewang
J
Han
Yong-Mahn
YM
Jang
Sung Key
SK
Shong
Minho
M
Kong
Young-Yun
YY
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
D018797:Cell Cycle Proteins; C527307:Crif1 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004247:DNA