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...

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Bibliographic Details
Published in:The EMBO journal 2008-02, Vol.27 (4), p.642-653
Main Authors: Kwon, Min-chul, Koo, Bon-Kyoung, Moon, Jin-Sook, Kim, Yoon-Young, Park, Ki Cheol, Kim, Nam-Shik, Kwon, Mi Yi, Kong, Myung-Phil, Yoon, Ki-Jun, Im, Sun-Kyoung, Ghim, Jaewang, Han, Yong-Mahn, Jang, Sung Key, Shong, Minho, Kong, Young-Yun
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Blastocyst - metabolism
Blastocyst - pathology
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line
Cell Proliferation
Cellular biology
Crif1
Deoxyribonucleic acid
DNA
DNA - metabolism
embryogenesis
Embryos
Female
Humans
Mice
Mice, Knockout
NIH 3T3 Cells
Pregnancy
Proteins
Signal transduction
STAT3
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Transcription, Genetic
transcriptional coactivator
tumorigenesis
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601986