| First Author | Lee J | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 6 | Pages | 4033-40 |
| PubMed ID | 22167182 | Mgi Jnum | J:181513 |
| Mgi Id | MGI:5311537 | Doi | 10.1074/jbc.M111.280065 |
| Citation | Lee J, et al. (2012) Autophagy suppresses interleukin-1beta (IL-1beta) signaling by activation of p62 degradation via lysosomal and proteasomal pathways. J Biol Chem 287(6):4033-40 |
| abstractText | ATG16L1 is an essential component of the autophagasome. The T300A allele of ATG16L1 is associated with the increased susceptibility to Crohn disease. In this study, we identified a novel function of ATG16L1, which suppresses signaling of the pro-inflammatory cytokine IL-1beta. Deletion of ATG16L1 in mouse embryonic fibroblasts significantly amplifies IL-1beta signal transduction cascades. This amplification is due to elevated p62 levels in ATG16L1-deficient cells. We found that ATG16L1 regulates p62 levels via both autolysosomal and proteasomal pathways. For proteasomal degradation, we found that Cullin-3 (Cul-3) is a E3 ubiquitin ligase of p62 and that ATG16L1 is essential for neddylation of Cul-3, a step required for Cul-3 activation. Taken together our data indicate that loss-of-function of ATG16L1 results in a hyper-responsiveness to the IL-1beta signaling because of the increased p62 level. |
