title: TRAF6-mediated ubiquitination of NEMO requires p62/sequestosome-1.
abstract: 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-κB in TNFα-stimulated cells and has been shown to be activated in response to interleukin-1β (IL-1β). Here we demonstrate that p62 interacts with NEMO, the regulatory subunit of the complex responsible for activation of NF-κB 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-κB activation following IL-1β stimulation. Together, these results indicate that p62 is an important intermediary in the NF-κB activation pathways implemented through non-degradative ubiquitination events.
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zotti
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Scudiero
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy; Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Pio
authors.initials: P
authors.lastname: Settembre
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ferravante
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy; Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Mazzone
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy; Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: D'Andrea
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Reale
authors.affiliation: Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy; College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: vito@unisannio.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Vito
authors.affiliation: Biogem, Via Camporeale, 83031 Ariano Irpino, Italy; Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Romania
authors.initials: R
authors.lastname: Stilo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491731:IKBKG protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D034741:RNA, Small Interfering; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D048029:TNF Receptor-Associated Factor 6; D051550:I-kappa B Kinase
keywords: IL-1β; NF-κB; TNFα; TRAF6; Ubiquitin; p62/sequestosome