The Atypical Protein Kinase C-interacting Protein p62 Is a Scaffold for NF-κB Activation by Nerve Growth Factor

• Published in: The Journal of biological chemistry Vol. 276; no. 11; pp. 7709 - 7712
• Main Authors: Wooten, Marie W., Seibenhener, M.Lamar, Mamidipudi, Vidya, Diaz-Meco, Maria T., Barker, Philip A., Moscat, Jorge
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.03.2001
• Subjects: IKK protein; p62 protein; protein kinase C-interacting protein; TRAF6 protein; TrkA protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C000869200

Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin receptors activates the transcription factor nuclear factor κB (NF-κB). Here we show that the atypical protein kinase C-interacting protein, p62, which binds TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts with p75 but not TrkA. We demonstrate the formation of a TRAF6-p62 complex that serves as a bridge linking both p75 and TrkA signaling. Of functional relevance, transfection of antisense p62-enhanced p75-mediated cell death and diminished NGF-induced differentiation occur through a mechanism involving inhibition of IKK activity. These findings reveal a new function for p62 as a common platform for communication of both p75-TRAF6 and TrkA signals. Moreover, we demonstrated that p62 serves as a scaffold for activation of the NF-κB pathway, which mediates NGF survival and differentiation responses.