Passa al contenuto
Merck

Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses.

eLife (2017-06-09)
Wei Liu, Jing Li, Weinan Zheng, Yingli Shang, Zhendong Zhao, Shanshan Wang, Yuhai Bi, Shuang Zhang, Chongfeng Xu, Ziyuan Duan, Lianfeng Zhang, Yue L Wang, Zhengfan Jiang, Wenjun Liu, Lei Sun
ABSTRACT

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS.

MATERIALI
N° Catalogo
Marchio
Descrizione del prodotto

Sigma-Aldrich
Anticorpo monoclonale ANTI-FLAG® M2, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Anti-c-Myc antibody produced in rabbit, ~0.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anticorpo monoclonale di coniglio anti-ubiquitina, Lys63-specifico, clone Apu3, clone Apu3, from rabbit
Sigma-Aldrich
Anti-RIG-I, clone 1C3 Antibody, clone 1C3, from mouse