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Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-κB activation via a negative feedback loop
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Elmetwali, Taha, Young, Lawrence S. and Palmer, Daniel H. (2014) Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-κB activation via a negative feedback loop. Cell Death and Disease , Volume 5 (Number 5). Article number e1213. doi:10.1038/cddis.2014.172 ISSN 2041-4889.
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Official URL: http://dx.doi.org/10.1038/cddis.2014.172
Abstract
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 NFκB-dependent manner. Knockdown of FAF1 prolonged CD40-induced NFκB, whereas overexpression of FAF1 suppressed CD40-induced NFκB activity and this required interaction of FAF1 with the CD40 receptor via its FID domain. Thus, we report a novel role for FAF1in regulating CD40-induced NFκB activation via a negative feedback loop. Loss of FAF1 function in certain human malignancies may contribute to oncogenesis through unchecked NFκB activation, and further understanding of this process may provide a biomarker of NFκB-targeted therapies for such malignancies.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||
| Library of Congress Subject Headings (LCSH): | Tumor necrosis factor -- Receptors, Tumors | ||||||||
| Journal or Publication Title: | Cell Death and Disease | ||||||||
| Publisher: | Nature Publishing Group | ||||||||
| ISSN: | 2041-4889 | ||||||||
| Official Date: | 8 May 2014 | ||||||||
| Dates: |
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| Volume: | Volume 5 | ||||||||
| Number: | Number 5 | ||||||||
| Article Number: | Article number e1213 | ||||||||
| DOI: | 10.1038/cddis.2014.172 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 27 December 2015 | ||||||||
| Date of first compliant Open Access: | 27 December 2015 | ||||||||
| Funder: | Cancer Research UK (CRUK), North West Cancer Research |
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