Ubiquitin activated tumor necrosis factor receptor associated factor‐6 (TRAF6) is recycled via deubiquitination

FEBS Letters

Whitehead, Alexander S¹  Jensen, Liselotte E¹ 

[1] Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, 156 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA

关键词: Interleukin-1;    Tumor necrosis factor associated factor-6;    Ubiquitination;    Deubiquitination;    Desensitization;    IκBα;    inhibitor of nuclear factor κB-α;    IL-1R;    IL-1 receptor;    IRAK1;    interleukin-1 receptor associated kinase-1;    RANKL;    receptor activator of NF-κB ligand;    TAK1;    transforming growth factor β activated kinase-1;    TLR;    Toll-like receptor;    TRAF6;    tumor necrosis factor receptor associated factor-6;   

DOI  :  10.1016/S0014-5793(03)00998-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ubiquitination of intermediates in the interleukin-1 (IL-1) signaling cascade plays an important role in activation and regulation of the pathway. Both IL-1 receptor associated kinase-1 (IRAK1) and inhibitor of nuclear factor κB-α (IκBα) are rapidly ubiquitinated and degraded. Tumor necrosis factor associated factor-6 (TRAF6) is an ubiquitin ligase that is activated by ubiquitination and a signaling intermediate between IRAK1 and IκBα. It is unknown whether activated TRAF6 is subsequently degraded. We show that in liver cells IL-1 stimulates TRAF6 poly-ubiquitination. In less than 1 h levels of non-modified TRAF6 return to levels near those observed prior to activation. TRAF6 cannot be reactivated in cells which have been pretreated with IL-1. This observation correlates with decreased levels of IRAK1 in IL-1 pretreated cells. The re-establishment of non-modified TRAF6 levels following activation does not require de novo protein synthesis, strongly suggesting that TRAF6 is recycled via deubiquitination. This indicates a unique mechanism of regulation of TRAF6 activity.

【 授权许可】

Unknown