Oncotarget

Research Papers:

Prox1 represses IL-2 gene expression by interacting with NFAT2

Shujie Zhang, Ning Yu, Linfang Wang, Yanfeng Liu, Yuying Kong, Jing Liu and Youhua Xie _

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Oncotarget. 2017; 8:69422-69434. https://doi.org/10.18632/oncotarget.17278

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Abstract

Shujie Zhang1,3,*, Ning Yu2,*, Linfang Wang3, Yanfeng Liu3, Yuying Kong3, Jing Liu3 and Youhua Xie3

1Eye Institute, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China

2Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai 200050, China

3Key Laboratory of Medical Molecular Virology (MOE and MOH), Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China

*These authors contributed equally to this work

Correspondence to:

Shujie Zhang, email: [email protected]

Youhua Xie, email: [email protected]

Keywords: gene regulation, prospero-related homeobox 1, repression, nuclear factor of activated T cells 2

Received: March 01, 2017     Accepted: April 11, 2017     Published: April 20, 2017

ABSTRACT

Interleukin-2 (IL-2) is critical for T lymphocyte activation and regulated by many transcriptional factors. Prospero-related homeobox 1 (Prox1) is a multifunctional transcription factor, which can work as either a transcriptional activator or repressor depending on the cellular and developmental environment. We previously reported the Prox1 expression in T cells, raising the possibility of Prox1 involvement in the regulation of T cell function and IL-2 production. Here we demonstrated that the Prox1 expression in CD4+ T cells was downregulated by T cell receptor (TCR) activation. Overexpression of Prox1 attenuated IL-2 production, while knockdown of endogenous Prox1 by small interfering RNA increased IL-2 expression. Mechanistically, we showed that Prox1 inhibited the IL-2 promoter activity, and associated with the minimal IL-2 promoter. Prox1 repressed the nuclear factor of activated T cells 2 (NFAT2)-dependent transactivation of IL-2 gene by physically binding to NFAT2. The N-terminal region of Prox1 was essential for the binding and repression. In summary, our findings established Prox1 as a negative regulator in IL-2 gene expression through the direct interaction with NFAT2.


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