First Author | Li J | Year | 2018 |
Journal | FASEB J | Volume | 32 |
Issue | 8 | Pages | 4096-4106 |
PubMed ID | 29485902 | Mgi Jnum | J:275601 |
Mgi Id | MGI:6307660 | Doi | 10.1096/fj.201700642RRR |
Citation | Li J, et al. (2018) NF-kappaB directly regulates beta-arrestin-1 expression and forms a negative feedback circuit in TNF-alpha-induced cell death. FASEB J 32(8):4096-4106 |
abstractText | beta-Arrestins (beta-arrestin-1 and -2) are multifunctional proteins that play important roles in the regulation of inflammation and cell survival that need to be tightly controlled; however, the mechanism that underlies their gene expression is largely unclear. Here, we demonstrate that beta-arrestin-1 is a transcriptional target of NF-kappaB. mRNA and protein levels of beta-arrestin-1 were up-regulated by NF-kappaB inducers. Inhibition of NF-kappaB prevented the up-regulation of beta-arrestin-1 mRNA, whereas activation of NF-kappaB led to increased beta-arrestin-1 expression. beta-Arrestin-1 promoter activity was consistently enhanced upon NF-kappaB activation as a result of the presence of a highly conserved kappaB site. beta-Arrestin-1, in turn, suppressed the transcriptional activity of NF-kappaB by interfering with the interaction between p65 and p50. beta-Arrestin-1-deficient mice displayed reduced TNF-alpha-induced cell death and increased expression of antiapoptotic genes. Reintroduction of beta-arrestin-1, but not its mutant, which is unable to interfere with the p65-p50 interaction, into beta-arrestin-deficient mouse embryonic fibroblasts partially restored sensitivity to TNF-alpha-induced cell death. These findings reveal NF-kappaB and beta-arrestin-1 to be key components of a negative feedback circuit that is necessary to regulate cell death.-Li, J., Guo, A., Wang, Q., Li, Y., Zhao, J., Lu, J., Pei, G. NF-kappaB directly regulates beta-arrestin-1 expression and forms a negative feedback circuit in TNF-alpha-induced cell death. |