Ran binding protein 9 (RanBPM) binds IFN-λR1 in the IFN-λ signaling pathway

Junwen Zhang; Xiaojie Cong; Jiajie Zhaoqiao; Xia Yang; Meng Li; Hong Chen; Ruifang Mi; Guishan Jin; Fusheng Liu; Bing-Ren Huang

doi:10.1007/s11427-017-9028-6

Ran binding protein 9 (RanBPM) binds IFN-λR1 in the IFN-λ signaling pathway

Sci China Life Sci. 2017 Sep;60(9):1030-1039. doi: 10.1007/s11427-017-9028-6. Epub 2017 May 24.

Authors

Junwen Zhang^{1

2}, Xiaojie Cong¹, Jiajie Zhaoqiao¹, Xia Yang¹, Meng Li¹, Hong Chen¹, Ruifang Mi², Guishan Jin², Fusheng Liu^{3

4}, Bing-Ren Huang⁵

Affiliations

¹ National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
² Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, 100050, China.
³ Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, 100050, China. liufushengs@hotmail.com.
⁴ Beijing Laboratory of Biomedical Materials, Beijing, 100050, China. liufushengs@hotmail.com.
⁵ National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China. huangbingren@hotmail.com.

PMID: 28547582
DOI: 10.1007/s11427-017-9028-6

Abstract

Like the type I interferons (IFNs), the recently discovered cytokine IFN-λ displays antiviral, antiproliferative, and proapoptotic activities, mediated by a heterodimeric IFN-λ receptor complex composed of a unique IFN-λR1 chain and the IL-10R2 chain. However, the molecular mechanism of the IFN-λ-regulated pathway remains unclear. In this study, we newly identified RAN-binding protein M (RanBPM) as a binding partner of IFN-λR1. The interaction between RanBPM and IFN-λR1 was identified with a glutathione S-transferase pull-down assay and coimmunoprecipitation experiments. IFN-λ1 stimulates this interaction and affects the cellular distribution of RanBPM. However, the interaction between RanBPM and IFN-λR1 does not correlate with their conserved TRAF6-binding sites. Furthermore, we also found that RanBPM is a scaffolding protein with a modulatory function that regulates the activities of IFN-stimulated response elements. Therefore, RanBPM plays a novel role in the IFN-λ-regulated signaling pathway.

Keywords: IFN-λ; IFN-λR1; RanBPM; interaction.

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Binding Sites
Cell Line, Transformed
Cell Line, Tumor
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism*
HEK293 Cells
Humans
Immunoprecipitation
Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism
Interferons
Interleukins / metabolism*
Intracellular Signaling Peptides and Proteins
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Protein Binding
Receptors, Cytokine / genetics
Receptors, Cytokine / metabolism*
Receptors, Interferon
Response Elements
Signal Transduction / genetics
Signal Transduction / physiology*
TNF Receptor-Associated Factor 6 / metabolism
Ubiquitination

Substances

Adaptor Proteins, Signal Transducing
Cytoskeletal Proteins
interferon-lambda, human
IFNLR1 protein, human
IRF9 protein, human
Interferon-Stimulated Gene Factor 3, gamma Subunit
Interleukins
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Ran binding protein 9
Receptors, Cytokine
Receptors, Interferon
TNF Receptor-Associated Factor 6
Tifab protein, human
Interferons