p62 serves as a shuttling factor for TrkA interaction with the proteasome
Autor: | Thangiah Geetha, Marie W. Wooten, Kiran Madura, Li Chen, M. Lamar Seibenhener |
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Rok vydání: | 2008 |
Předmět: |
Sequestosome-1 Protein
Scaffold protein Proteasome Endopeptidase Complex animal structures media_common.quotation_subject Biophysics Tropomyosin receptor kinase A Biochemistry Article Mice Ubiquitin Heat shock protein Animals Humans Receptor trkA Internalization Molecular Biology Heat-Shock Proteins Adaptor Proteins Signal Transducing media_common Mice Knockout Neurons biology Intracellular Signaling Peptides and Proteins Ubiquitination Protein turnover Brain Cell Biology Protein Structure Tertiary Cell biology nervous system Proteasome biology.protein |
Zdroj: | Biochemical and Biophysical Research Communications. 374:33-37 |
ISSN: | 0006-291X |
Popis: | The scaffold protein p62 is involved in internalization and trafficking of TrkA. The receptor is deubiquitinated by the proteasomes prior to degradation by lysosomes. Here we demonstrate that p62 serves as a shuttling protein for interaction of ubiquitinated TrkA with Rpt1, one of the six ATPases of 19S regulatory particle of the 26S proteasome. In p62(-/-) mouse brain TrkA failed to interact with the Rpt1. The interaction of TrkA with Rpt1 was reduced in proteasomes isolated from p62(-/-) brain, but was restored by addition of p62. The UBA domain of p62 interacts with TrkA and its PB1/UbL domain with AAA-ATPase cassette in the C-terminal region of Rpt1. Last, neurotrophin-dependent turnover of TrkA was impaired by reduction in the level of p62. These findings reveal that p62 serves as a shuttling factor for interaction of ubiquitinated substrates with the proteasome and could promote localized protein turnover in neurons. |
Databáze: | OpenAIRE |
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