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

doi:10.1038/sj.emboj.7601986

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 journal › Article › peer-review

52 Scopus citations

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 language	English (US)
Pages (from-to)	642-653
Number of pages	12
Journal	EMBO Journal
Volume	27
Issue number	4
DOIs	https://doi.org/10.1038/sj.emboj.7601986
State	Published - Feb 20 2008
Externally published	Yes

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)

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10.1038/sj.emboj.7601986

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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.",

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

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T1 - Crif1 is a novel transcriptional coactivator of STAT3

AU - Kwon, Min Chul

AU - Koo, Bon Kyoung

AU - Moon, Jin Sook

AU - Kim, Yoon Young

AU - Park, Ki Cheol

AU - Kim, Nam Shik

AU - Kwon, Mi Yi

AU - Kong, Myung Phil

AU - Yoon, Ki Jun

AU - Im, Sun Kyoung

AU - Ghim, Jaewang

AU - Han, Yong Mahn

AU - Jang, Sung Key

AU - Shong, Minho

AU - Kong, Young Yun

PY - 2008/2/20

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N2 - 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.

AB - 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.

KW - Crif1

KW - Embryogenesis

KW - STAT3

KW - Transcriptional coactivator

KW - Tumorigenesis

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Crif1 is a novel transcriptional coactivator of STAT3

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