XIAP Interacts with and Regulates the Activity of FAF1
| Autor: | Manuel Nieto-Díaz, Rodrigo M. Maza, R Navarro-Ruiz, Ángela del Águila, Mónica Yunta, Dan Lindholm, Marcos Javier Caballero-Lopez, David Reigada, Wolfgang Pita-Thomas, Teresa Muñoz-Galdeano |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Apoptosis X-Linked Inhibitor of Apoptosis Protein Inhibitor of apoptosis 03 medical and health sciences 0302 clinical medicine Ubiquitin Humans Molecular Biology Caspase Adaptor Proteins Signal Transducing Binding Sites biology Chemistry NF-kappa B Ubiquitination Cell Biology XIAP HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research Signal transduction Apoptosis Regulatory Proteins HeLa Cells Protein Binding |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864:1335-1348 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2017.04.006 |
| Popis: | Cell death depends on the balance between the activities of pro- and anti-apoptotic factors. X-linked inhibitor of apoptosis protein (XIAP) plays an important role in the cytoprotective process by inhibiting the caspase cascade and regulating pro-survival signaling pathways. While searching for novel interacting partners of XIAP, we identified Fas-associated factor 1 (FAF1). Contrary to XIAP, FAF1 is a pro-apoptotic factor that also regulates several signaling pathways in which XIAP is involved. However, the functional relationship between FAF1 and XIAP is unknown. Here, we describe a new interaction between XIAP and FAF1 and describe the functional implications of their opposing roles in cell death and NF-κB signaling. Our results clearly demonstrate the interaction of XIAP with FAF1 and define the specific region of the interaction. We observed that XIAP is able to block FAF1-mediated cell death by interfering with the caspase cascade and directly interferes in NF-κB pathway inhibition by FAF1. Furthermore, we show that XIAP promotes ubiquitination of FAF1. Conversely, FAF1 does not interfere with the anti-apoptotic activity of XIAP, despite binding to the BIR domains of XIAP; however, FAF1 does attenuate XIAP-mediated NF-κB activation. Altered expression of both factors has been implicated in degenerative and cancerous processes; therefore, studying the balance between XIAP and FAF1 in these pathologies will aid in the development of novel therapies. |
| Databáze: | OpenAIRE |
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