TRAF6 is autoinhibited by an intramolecular interaction which is counteracted by trans-ubiquitination.
J Cell Biochem
; 110(3): 763-71, 2010 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-20512936
The tumor necrosis factor (TNF) receptor associated factor (TRAF) class of intracellular signal transducers is responsible for mediating many of the activation events initiated by TNF receptor (TNFR) and Toll-like/Interleukin-1, -17, and -18 receptor (TIR) families. Investigation of the mechanism by which TRAF6 is activated has demonstrated that two critical domains of the molecule required for activation and downstream signaling are involved in an interaction which renders the molecule inactive and structurally closed, as well as incapable of auto-ubiquitination. Contrary to its assumed role as a direct mediator of protein-protein interaction, TRAF auto-ubiquitination is a means of sustaining an open conformation active in downstream signaling. Furthermore, the inferred cis-function of TRAF auto-ubiquitination is now demonstrated to act in trans and requires both the RING-Zinc (RZ) fingers region and coiled-coil domain. We also observed that both the RZ fingers region and the MATH domain are targets for ubiquitination. Although TRAF6 ubiquitination has emerged as a hallmark of activation, trans-ubiquitination induced by two TRAF6 muteins is insufficient for NF-kappaB activation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor 6 Asociado a Receptor de TNF
/
Ubiquitinación
Límite:
Humans
Idioma:
En
Revista:
J Cell Biochem
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos