TRAF6-mediated ubiquitination of NEMO requires p62/sequestosome-1

The atypical protein kinase C-interacting protein p62/sequestosome-1 (p62) has emerged as a crucial molecule in a variety of cellular functions due to its involvement in various signaling mechanisms. p62 has been implicated in the activation of NF-kappa B in TNF alpha-stimulated cells and has been shown to be activated in response to interleukin-1 beta (IL-1 beta). Here we demonstrate that p62 interacts with NEMO, the regulatory subunit of the complex responsible for activation of NF-kappa B transcription factor. Depletion of p62 obtained through a short interfering RNA targeting p62 mRNA abrogated TRAF6 capacity to promote NEMO ubiquitination and severely impairs NF-kappa B activation following IL-1 beta stimulation. Together, these results indicate that p62 is an important intermediary in the NF-kappa B activation pathways implemented through non-degradative ubiquitination events. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.