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IFITM1 plays an essential role in the antiproliferative action of interferon-γ

Oncogene volume 26, pages 594–603 (2007)Cite this article

Abstract

Interferon-γ (IFN-γ) is a pleiotropic cytokine involved in antiproliferative and anti-virus responses, immune surveillance and tumor suppression. These biological responses to IFN-γ are mainly mediated by the regulation of gene expression. It has been reported that growth-inhibitory role of IFN-γ is dependent on activation of signal transducers and activators of transcription 1 (STAT1); however, the molecular basis downstream of STAT1 remains unclear. Here, we report that an IFN-γ-induced gene, interferon-induced transmembrane protein 1 (IFITM1), plays a key role in the antiproliferative action of IFN-γ. Overexpression of IFITM1 negatively regulated cell growth, whereas suppression of IFITM1 blocked the antiproliferative effect of IFN-γ, accelerated the cell growth rate and conferred tumorigenicity to a non-malignant hepatocyte in nude mice. Further, IFITM1 could inhibit the activity of extracellular signal-regulated kinase, enhance the transcriptional activity of p53 and stabilize the p53 protein by inhibiting p53 phosphorylation on Thr55. Suppression of p53 reduced the growth-inhibitory capacity of both IFITM1 and IFN-γ. Therefore, these findings indicated that the antiproliferative action of IFN-γ requires the induction of IFITM1, and provided a crosstalk between two well-known signaling mediators, STAT1 and p53, both of which play critical roles in tumor suppression.

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Acknowledgements

We thank Dr B Vogelstein (Johns Hopkins University, Baltimore, MD, USA) for p53 reporter plasmid, Dr Xin Wu (Liver Cancer Institute, Zhongshan Hospital, Medical Center of Fudan University, Shanghai) for clinical HCC samples, and Chaochen Wang and Zheng Qin for technical assistances. This work was support by Chinese High-Tech R&D Program (863)-2001AA231011 and-20022Z2002.

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  1. State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    G Yang, Y Xu, X Chen & G Hu

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Correspondence to G Hu.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Yang, G., Xu, Y., Chen, X. et al. IFITM1 plays an essential role in the antiproliferative action of interferon-γ. Oncogene 26, 594–603 (2007). https://doi.org/10.1038/sj.onc.1209807

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