SKP2 attenuates NF-?B signaling by mediating IKK? degradation through autophagy.
NF-?B 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-?B activation is suppressed by an F-box protein, S-phase kinase associated protein 2 (SKP2). SKP2 ... deficiency enhanced NF-?B activation as well as the production of inflammatory cytokines. In addition, SKP2 potently blocked the NF-?B activation at the I?B kinase (IKK) level. Mechanistic study further revealed that SKP2 functions as an adaptor to promote an interaction between active IKK? and the autophagic cargo receptor p62 to mediate IKK? degradation via selective autophagy. These findings identify a previously unrecognized role of SKP2 in NF-?B activation by which SKP2 acts as a secondary receptor to assist IKK? delivery to autophagosomes for degradation in a p62-dependent manner.
Mesh Terms:
Autophagy, Gene Knockout Techniques, HEK293 Cells, Humans, I-kappa B Kinase, NF-kappa B, Proteolysis, S-Phase Kinase-Associated Proteins, Signal Transduction
Autophagy, Gene Knockout Techniques, HEK293 Cells, Humans, I-kappa B Kinase, NF-kappa B, Proteolysis, S-Phase Kinase-Associated Proteins, Signal Transduction
J Mol Cell Biol
Date: Dec. 01, 2017
PubMed ID: 29474632
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