| First Author | Hiraoka Y | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 370 |
| Issue | 1 | Pages | 154-8 |
| PubMed ID | 18355445 | Mgi Jnum | J:134275 |
| Mgi Id | MGI:3785216 | Doi | 10.1016/j.bbrc.2008.03.050 |
| Citation | Hiraoka Y, et al. (2008) Ectodomain shedding of TNF-alpha is enhanced by nardilysin via activation of ADAM proteases. Biochem Biophys Res Commun 370(1):154-8 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) is released from cells by proteolytic cleavage of a membrane-anchored precursor. The TNF-alpha-converting enzyme (TACE/ADAM17) is the major sheddase for ectodomain shedding of TNF-alpha. At present, however, it is poorly understood how its catalytic activity is regulated. Here, we show that nardilysin (N-arginine dibasic convertase; NRDc) enhanced TNF-alpha shedding. In a cell-based shedding assay, expression of NRDc synergistically enhanced TACE-induced TNF-alpha shedding. A peptide cleavage assay in vitro showed that recombinant NRDc enhances the cleavage of TNF-alpha induced by TACE. Notably, co-incubation of NRDc completely reversed the inhibitory effect of a physiological concentration of salt on TACE's activity in vitro. Overexpression of NRDc in TACE-deficient fibroblasts resulted in an increase in the amount of TNF-alpha released. Co-expression of NRDc with ADAM10 promoted the release compared with the sole expression of ADAM10. These results suggested that NRDc enhances TNF-alpha shedding through activation of not only TACE but ADAM10. Our results indicate the involvement of NRDc in ectodomain shedding of TNF-alpha, which may be a novel target for anti-inflammatory therapies. |
