Advanced Search

Submit Online

Articles

< Previous         Next >  
SKP2 attenuates NF-κB signaling by mediating IKKβ degradation through autophagy Free
Kunpeng Liu 1,2,† , Lei Zhang 1,† , Qiang Zhao 2,† , Zhiyao Zhao 1 , Feng Zhi 3,* , Yunfei Qin 4,* ,and Jun Cui 1,*
1 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University,Guangzhou 510006, China
2 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
3 Modern Medical Research Center, Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, China
4 Guangdong Provincial Key Laboratory of Liver Disease, Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
† These authors contributed equally to this work. *Correspondence to:Feng Zhi, E-mail: danielzhif@suda.edu.cn; Yunfei Qin, E-mail: qinyunfei@163.com; Jun Cui, E-mail: cuij5@mail.sysu.edu.cn
J Mol Cell Biol, Volume 10, Issue 3, June 2018, 205-215,  https://doi.org/10.1093/jmcb/mjy012
Keyword: SKP2, IKKβ, NF-κB activation, autophagy, inflammation

NF-κB signaling controls a large set of physiological processes ranging from inflammatory responses to cell death. Its activation is tightly regulated through controlling the activity and stability of multiple signaling components. Here, we identify that NF-κB activation is suppressed by an F-box protein, S-phase kinase associated protein 2 (SKP2). SKP2 deficiency enhanced NF-κB activation as well as the production of inflammatory cytokines. In addition, SKP2 potently blocked the NF-κB activation at the IκB kinase (IKK) level. Mechanistic study further revealed that SKP2 functions as an adaptor to promote an interaction between active IKKβ and the autophagic cargo receptor p62 to mediate IKKβ degradation via selective autophagy. These findings identify a previously unrecognized role of SKP2 in NF-κB activation by which SKP2 acts as a secondary receptor to assist IKKβ delivery to autophagosomes for degradation in a p62-dependent manner.


Volume 10, Issue 3
June 2018