Crif1 is a Novel Transcriptional Coactivator of STAT3

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2008 Jan 18

PMID 18200042

Citations 39

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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The Downregulation of CRIF1 Exerts Antitumor Effects Partially via TP53-Induced Glycolysis and Apoptosis Regulator Induction in BT549 Breast Cancer Cells.

Piao S, Kim S, Vu G, Kim M, Lee E, Jeon B Cancers (Basel). 2024; 16(23).

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Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism.

Heo J, Park A, Lee M, Ryu M, Kim Y, Jang Y Mol Psychiatry. 2023; 28(10):4474-4484.

PMID: 37648779 DOI: 10.1038/s41380-023-02234-5.

Multifunctions of CRIF1 in cancers and mitochondrial dysfunction.

Jiang Y, Xiang Y, Lin C, Zhang W, Yang Z, Xiang L Front Oncol. 2022; 12:1009948.

PMID: 36263222 PMC: 9574215. DOI: 10.3389/fonc.2022.1009948.

Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failure.

Hong H, Joung K, Kim Y, Choi M, Kang S, Kim J Exp Mol Med. 2022; 54(7):932-945.

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