| First Author | Zhang P | Year | 2005 |
| Journal | EMBO Rep | Volume | 6 |
| Issue | 6 | Pages | 531-7 |
| PubMed ID | 15905851 | Mgi Jnum | J:98834 |
| Mgi Id | MGI:3580027 | Doi | 10.1038/sj.embor.7400433 |
| Citation | Zhang P, et al. (2005) Activation of IKK by thymosin alpha1 requires the TRAF6 signalling pathway. EMBO Rep 6(6):531-7 |
| abstractText | Thymosin alpha1 (Talpha1) is noted for its immunomodulatory activities and therapeutic potential in treatment of infectious diseases and cancer. However, the molecular mechanism of its effectiveness is not completely understood. Here, we report that Talpha1 induces interleukin (IL)-6 expression through the IkappaB kinase (IKK) and nuclear factor-kappaB (NF-kappaB) pathway. Using IKKbeta-deficient bone-marrow-derived macrophages and mouse embryo fibroblasts (MEFs), we show that IKKbeta is essential for IKK and NF-kappaB activation as well as efficient IL-6 induction. Further analysis using tumour necrosis factor receptor-associated factor 6 (TRAF6)-deficient MEFs shows that TRAF6 is crucial for activation of IKK and induction of IL-6 by Talpha1. Intriguingly, Talpha1 triggers protein kinase C (PKC)iota/zeta activation, which is TRAF6 dependent and involves IKK. In addition, Talpha1 induces the formation of a signalsome composed of TRAF6, p62 and PKCiota/zeta as well as IKK. Thus, our study identifies Talpha1 as a unique activator of the TRAF6 signal pathway and provides a cohesive interpretation of the molecular basis of the therapeutic utility of Talpha1. |
