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NIRF, a novel ubiquitin ligase, interacts with hepatitis B virus core protein and promotes its degradation

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Abstract

Hepatitis B virus (HBV) core protein (HBc) is a major component of viral nucleocapsid and a multifunctional protein involved in viral maturation and release. It is unstable and present in cells at low level because of K96 lysine residue, which is a ubiquitin acceptor site. Np95/ICBP90-like RING finger protein (NIRF) has auto-ubiquitination activity which is the hallmark of a ubiquitin ligase. In the present study, ubiquitin ligase, NIRF, binds to HBc and leads to the proteasome-mediated degradation of HBc in vivo. NIRF down-regulates HBc protein level, resulting in the decrease of the amount of HBV particles in supernatant of HepG2.2.15 cells. However knockdown of NIRF significantly increases endogenous HBc protein level, leading to HBV release. The results reveal that NIRF interacts with HBc and promotes the degradation of HBc in vivo. The pathway of NIRF-mediated ubiquitin–proteasome affects the release of HBV particles by controlling the amounts of HBc. It indicates that NIRF may participate in the maturation of HBV.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Nos. 30872248), Chongqing Science Commission (CSTC, 2008BB5400) and Chongqing Municipal Education Commission (KJ080326). We are grateful to Professor OU JH (University of Southern California) for pCMV-core.

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Authors and Affiliations

  1. Key Laboratory of Clinical Laboratory Diagnostics of Ministry of Education, Faculty of Laboratory Medicine, Department of Cell Biology and Medical Genetics, Chongqing Medical University, No. 1, Medical College Road, Chongqing, 400016, China

    Guanhua Qian, Fangmin Jin, Yan Yang & Changzhu Duan

  2. Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China

    Guanhua Qian, Fangmin Jin, Yan Yang & Changzhu Duan

  3. Basic Medical Experimental Teaching Centre, Chongqing Medical University, Chongqing, China

    Huimin Peng

  4. Beijing Proteome Research Center, Beijing, China

    Lei Chang & Huimin Peng

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  1. Guanhua Qian
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  2. Fangmin Jin
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  3. Lei Chang
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  4. Yan Yang
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  5. Huimin Peng
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  6. Changzhu Duan
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Correspondence to Changzhu Duan.

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Qian, G., Jin, F., Chang, L. et al. NIRF, a novel ubiquitin ligase, interacts with hepatitis B virus core protein and promotes its degradation. Biotechnol Lett 34, 29–36 (2012). https://doi.org/10.1007/s10529-011-0751-0

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  • DOI: https://doi.org/10.1007/s10529-011-0751-0

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