Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-kappa B activation via a negative feedback loop

作者：Elmetwali T; Young L S; Palmer D H^*

来源：Cell Death & Disease, 2014, 5(5): e1213.

DOI：10.1038/cddis.2014.172

• CD40
• FAF1
• NF kappa B

CD40-induced signalling through ligation with its natural ligand (CD40L/CD154) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor. Here, we applied the yeast two-hybrid system to examine whether other proteins can interact with CD40. Fas-Associated Factor 1(FAF1) was isolated from a HeLa cDNA library using the CD40 cytoplasmic tail (216-278 aa) as a bait construct. FAF1 was able to interact with CD40 both in vitro and in vivo. The FAF1 N-terminal domain was sufficient to bind CD40 and required the TRAF6-binding domain within the cytoplasmic tail of CD40 for binding. CD40 ligation induced FAF1 expression in an NF kappa B-dependent manner. Knockdown of FAF1 prolonged CD40-induced NF kappa B, whereas overexpression of FAF1 suppressed CD40-induced NF kappa B activity and this required interaction of FAF1 with the CD40 receptor via its FID domain. Thus, we report a novel role for FAF1 in regulating CD40-induced NF kappa B activation via a negative feedback loop. Loss of FAF1 function in certain human malignancies may contribute to oncogenesis through unchecked NF kappa B activation, and further understanding of this process may provide a biomarker of NF kappa B-targeted therapies for such malignancies.

• 出版日期2014-5