Optineurin and NEMO: a potential novel interplay to fine tune NF-κB activation upon TCR engagement. (IRM10P.742)

Abstract

Abstract Optineurin (OPTN) is a homolog of NF-κB essential-modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) complex. Dysregulation of OPTN has been linked to several neurodegenerative diseases. Although OPTN shares with NEMO a high degree of homology, OPTN is not part of the same high-molecular weight complex containing IKKα and IKKβ. Although, OPTN cannot substitute for NEMO during (LPS)-induced NF-κB activation, OPTN negatively regulates TNF-α induced NF-κB activation by competing with NEMO for ubiquitinated proteins. We have investigated the potential role of OPTN during TCR induced NF-κB activation. OPTN overexpression down-regulates TCR-induced NF-κB activation in a dose-dependent manner. Furthermore we observed a transient loss of OPTN after stimulation of T cell lines or primary human or murine T cells. We further determined that the transient loss of OPTN upon TCR stimulation does not seem to be due to proteosomal degradation, suggesting a potential involvement of lysosomal degradation pathway. The present study provides new information regarding the role of OPTN in regulating NF-κB during TCR stimulation, thus revealing the possible importance of OPTN during inflammation and/or autoimmune diseases.