| First Author | Chen M | Year | 2020 |
| Journal | Adv Sci (Weinh) | Volume | 7 |
| Issue | 1 | Pages | 1901261 |
| PubMed ID | 31921549 | Mgi Jnum | J:285401 |
| Mgi Id | MGI:6393109 | Doi | 10.1002/advs.201901261 |
| Citation | Chen M, et al. (2020) TRIM14 Promotes Noncanonical NF-kappaB Activation by Modulating p100/p52 Stability via Selective Autophagy. Adv Sci (Weinh) 7(1):1901261 |
| abstractText | The noncanonical NF-kappaB signaling pathway plays a critical role in a variety of biological functions including chronic inflammation and tumorigenesis. Activation of noncanonical NF-kappaB signaling largely relies on the abundance as well as the processing of the NF-kappaB family member p100/p52. Here, TRIM14 is identified as a novel positive regulator of the noncanonical NF-kappaB signaling pathway. TRIM14 promotes noncanonical NF-kappaB activation by targeting p100/p52 in vitro and in vivo. Furthermore, a mechanistic study shows that TRIM14 recruits deubiquitinase USP14 to cleave the K63-linked ubiquitin chains of p100/p52 at multiple sites, thereby preventing p100/p52 from cargo receptor p62-mediated autophagic degradation. TRIM14 deficiency in mice significantly impairs noncanonical NF-kappaB-mediated inflammatory responses as well as acute colitis and colitis-associated colon cancer development. Taken together, these findings establish the TRIM14-USP14 axis as a crucial checkpoint that controls noncanonical NF-kappaB signaling and highlight the crosstalk between autophagy and innate immunity. |
