This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seibenhener, M. L.
Right arrow Articles by Wooten, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seibenhener, M. L.
Right arrow Articles by Wooten, M. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2004, p. 8055-8068, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.8055-8068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Sequestosome 1/p62 Is a Polyubiquitin Chain Binding Protein Involved in Ubiquitin Proteasome Degradation

M. Lamar Seibenhener,1 Jeganathan Ramesh Babu,1 Thangiah Geetha,1 Hing C. Wong,2 N. Rama Krishna,2 and Marie W. Wooten*

Program in Cell and Molecular Biosciences, Department of Biological Sciences, Auburn University, Auburn,1 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama2

Received 12 February 2004/ Returned for modification 22 March 2004/ Accepted 23 June 2004

Herein, we demonstrate that the ubiquitin-associated (UBA) domain of sequestosome 1/p62 displays a preference for binding K63-polyubiquitinated substrates. Furthermore, the UBA domain of p62 was necessary for aggregate sequestration and cell survival. However, the inhibition of proteasome function compromised survival in cells with aggregates. Mutational analysis of the UBA domain reveals that the conserved hydrophobic patch MGF as well as the conserved leucine in helix 2 are necessary for binding polyubiquitinated proteins and for sequestration-aggregate formation. We report that p62 interacts with the proteasome by pull-down assay, coimmunoprecipitation, and colocalization. Depletion of p62 levels results in an inhibition of ubiquitin proteasome-mediated degradation and an accumulation of ubiquitinated proteins. Altogether, our results support the hypothesis that p62 may act as a critical ubiquitin chain-targeting factor that shuttles substrates for proteasomal degradation.

* Corresponding author. Mailing address: Dept. of Biological Sciences, 331 Funchess Hall, Auburn University, Auburn, AL 36849. Phone: (334) 844-9226. Fax: (334) 844-9234. E-mail: wootemw{at}auburn.edu.

Molecular and Cellular Biology, September 2004, p. 8055-8068, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.8055-8068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zheng, Y. T., Shahnazari, S., Brech, A., Lamark, T., Johansen, T., Brumell, J. H. (2009). The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway. J. Immunol. 183: 5909-5916 [Abstract] [Full Text]  
  • Chamoux, E., Couture, J., Bisson, M., Morissette, J., Brown, J. P., Roux, S. (2009). The p62 P392L Mutation Linked to Paget's Disease Induces Activation of Human Osteoclasts. Mol. Endocrinol. 23: 1668-1680 [Abstract] [Full Text]  
  • Kim, J. Y., Ozato, K. (2009). The Sequestosome 1/p62 Attenuates Cytokine Gene Expression in Activated Macrophages by Inhibiting IFN Regulatory Factor 8 and TNF Receptor-Associated Factor 6/NF-{kappa}B Activity. J. Immunol. 182: 2131-2140 [Abstract] [Full Text]  
  • Wang, Y., Meriin, A. B., Zaarur, N., Romanova, N. V., Chernoff, Y. O., Costello, C. E., Sherman, M. Y. (2009). Abnormal proteins can form aggresome in yeast: aggresome-targeting signals and components of the machinery. FASEB J. 23: 451-463 [Abstract] [Full Text]  
  • Rodriguez-Navarro, J. A., Gomez, A., Rodal, I., Perucho, J., Martinez, A., Furio, V., Ampuero, I., Casarejos, M. J., Solano, R. M., de Yebenes, J. G., Mena, M. A. (2008). Parkin deletion causes cerebral and systemic amyloidosis in human mutated tau over-expressing mice. Hum Mol Genet 17: 3128-3143 [Abstract] [Full Text]  
  • Shvets, E., Fass, E., Scherz-Shouval, R., Elazar, Z. (2008). The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes. J. Cell Sci. 121: 2685-2695 [Abstract] [Full Text]  
  • Ferrer, I., Santpere, G., van Leeuwen, F. W. (2008). Argyrophilic grain disease. Brain 131: 1416-1432 [Abstract] [Full Text]  
  • Kawai, K., Saito, A., Sudo, T., Osada, H. (2008). Specific Regulation of Cytokine-Dependent p38 MAP Kinase Activation by p62/SQSTM1. J Biochem 143: 765-772 [Abstract] [Full Text]  
  • Wooten, M. W., Geetha, T., Babu, J. R., Seibenhener, M. L., Peng, J., Cox, N., Diaz-Meco, M.-T., Moscat, J. (2008). Essential Role of Sequestosome 1/p62 in Regulating Accumulation of Lys63-ubiquitinated Proteins. J. Biol. Chem. 283: 6783-6789 [Abstract] [Full Text]  
  • Long, J., Gallagher, T. R. A., Cavey, J. R., Sheppard, P. W., Ralston, S. H., Layfield, R., Searle, M. S. (2008). Ubiquitin Recognition by the Ubiquitin-associated Domain of p62 Involves a Novel Conformational Switch. J. Biol. Chem. 283: 5427-5440 [Abstract] [Full Text]  
  • Sumimoto, H., Kamakura, S., Ito, T. (2007). Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants. Sci Signal 2007: re6-re6 [Abstract] [Full Text]  
  • Gal, J., Strom, A.-L., Kilty, R., Zhang, F., Zhu, H. (2007). p62 Accumulates and Enhances Aggregate Formation in Model Systems of Familial Amyotrophic Lateral Sclerosis. J. Biol. Chem. 282: 11068-11077 [Abstract] [Full Text]  
  • Kaniuk, N. A., Kiraly, M., Bates, H., Vranic, M., Volchuk, A., Brumell, J. H. (2007). Ubiquitinated-Protein Aggregates Form in Pancreatic {beta}-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy. Diabetes 56: 930-939 [Abstract] [Full Text]  
  • Rolland, P., Madjd, Z., Durrant, L., Ellis, I. O, Layfield, R., Spendlove, I. (2007). The ubiquitin-binding protein p62 is expressed in breast cancers showing features of aggressive disease. Endocr Relat Cancer 14: 73-80 [Abstract] [Full Text]  
  • Yip, K. H.M., Feng, H., Pavlos, N. J., Zheng, M. H., Xu, J. (2006). p62 Ubiquitin Binding-Associated Domain Mediated the Receptor Activator of Nuclear Factor-{kappa}B Ligand-Induced Osteoclast Formation: A New Insight into the Pathogenesis of Paget's Disease of Bone. Am. J. Pathol. 169: 503-514 [Abstract] [Full Text]  
  • Wang, K. Z. Q., Wara-Aswapati, N., Boch, J. A., Yoshida, Y., Hu, C.-D., Galson, D. L., Auron, P. E. (2006). TRAF6 activation of PI 3-kinase-dependent cytoskeletal changes is cooperative with Ras and is mediated by an interaction with cytoplasmic Src. J. Cell Sci. 119: 1579-1591 [Abstract] [Full Text]  
  • Kim, I., Rao, H. (2006). What's Ub Chain Linkage Got to Do with It?. Sci Signal 2006: pe18-pe18 [Abstract] [Full Text]  
  • Meller, R., Cameron, J. A., Torrey, D. J., Clayton, C. E., Ordonez, A. N., Henshall, D. C., Minami, M., Schindler, C. K., Saugstad, J. A., Simon, R. P. (2006). Rapid Degradation of Bim by the Ubiquitin-Proteasome Pathway Mediates Short-term Ischemic Tolerance in Cultured Neurons. J. Biol. Chem. 281: 7429-7436 [Abstract] [Full Text]  
  • Wooten, M. W., Geetha, T., Seibenhener, M. L., Babu, J. R., Diaz-Meco, M. T., Moscat, J. (2005). The p62 Scaffold Regulates Nerve Growth Factor-induced NF-{kappa}B Activation by Influencing TRAF6 Polyubiquitination. J. Biol. Chem. 280: 35625-35629 [Abstract] [Full Text]  
  • Lundgren, J., Masson, P., Mirzaei, Z., Young, P. (2005). Identification and Characterization of a Drosophila Proteasome Regulatory Network. Mol. Cell. Biol. 25: 4662-4675 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»