QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 4 March 2003
doi: 10.1242/jcs.00370

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00370v1 116/9/1707    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arabi, A. Articles by Wright, A. P. H. Search for Related Content PubMed PubMed Citation Articles by Arabi, A. Articles by Wright, A. P. H.

Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels

Azadeh Arabi^1,2,*,, Cecilia Rustum^1,3,*, Einar Hallberg¹ and Anthony P. H. Wright^1,2

¹ Natural Sciences Section, Södertörns University College, S-141 89 Huddinge, Sweden
² Department of Biosciences, Karolinska Institute, S-141 57 Huddinge, Sweden
³ Department of Neurochemistry and Neurotoxicology, Stockholms University, S-106 91 Stockholm, Sweden

Author for correspondence (e-mail: azadeh.arabi{at}sh.se)

Accepted 15 January 2003

c-Myc is a predominately nuclear transcription factor that is a substrate for rapid turnover by the proteasome system. Cancer-related mutations in c-Myc lead to defects in its degradation and thereby contribute to the increase in its cellular level that is associated with the disease. Little is known about the mechanisms that target c-Myc to the proteasomes. By using a GFP fusion protein and live analysis we show that c-Myc shuttles between the nucleus and cytoplasm and thus it could be degraded in either compartment. Strikingly, at elevated levels of expression c-Myc accumulates at nucleoli in some cells, consistent with saturation of a nucleolus-associated degradation system in these cells. This idea is further supported by the observation that proteasome inhibitor treatment causes accumulation of c-Myc at the nucleoli of essentially all cells. Under these conditions c-Myc is relatively stably associated with the nucleolus, as would be expected if the nucleolus functions as a sequestration/degradation site for excess c-Myc. Furthermore, during elevated c-Myc expression or proteasome inhibition, nucleoli that are associated with c-Myc also accumulate proteasomes. c-Myc and proteasomes co-localise in intranucleolar regions distinct from the dense fibrillar component of the nucleolus. Based on these results we propose a model for c-Myc downregulation where c-Myc is sequestered at the nucleoli. Sequestration of c-Myc is accompanied by recruitment of proteasomes and may lead to subsequent degradation.

Key words: Transcription factor, Proteasome inhibitor, Degradation, Stability, Photobleaching

This article has been cited by other articles:

				M. Eilers and R. N. Eisenman Myc's broad reach Genes & Dev., October 15, 2008; 22(20): 2755 - 2766. [Abstract] [Full Text] [PDF]

				K. A. Tworkowski, A. A. Chakraborty, A. V. Samuelson, Y. R. Seger, M. Narita, G. J. Hannon, S. W. Lowe, and W. P. Tansey Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc PNAS, April 22, 2008; 105(16): 6103 - 6108. [Abstract] [Full Text] [PDF]

				D. A. Stavreva, M. Kawasaki, M. Dundr, K. Koberna, W. G. Muller, T. Tsujimura-Takahashi, W. Komatsu, T. Hayano, T. Isobe, I. Raska, et al. Potential Roles for Ubiquitin and the Proteasome during Ribosome Biogenesis. Mol. Cell. Biol., July 1, 2006; 26(13): 5131 - 5145. [Abstract] [Full Text] [PDF]

				J. F. Nabhan and P. Ribeiro The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization J. Biol. Chem., June 9, 2006; 281(23): 16099 - 16107. [Abstract] [Full Text] [PDF]

				A. von Mikecz The nuclear ubiquitin-proteasome system J. Cell Sci., May 15, 2006; 119(10): 1977 - 1984. [Abstract] [Full Text] [PDF]

				V. Torrano, J. Navascues, F. Docquier, R. Zhang, L. J. Burke, I. Chernukhin, D. Farrar, J. Leon, M. T. Berciano, R. Renkawitz, et al. Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism J. Cell Sci., May 1, 2006; 119(9): 1746 - 1759. [Abstract] [Full Text] [PDF]

				T. D. Rockel, D. Stuhlmann, and A. von Mikecz Proteasomes degrade proteins in focal subdomains of the human cell nucleus J. Cell Sci., November 15, 2005; 118(22): 5231 - 5242. [Abstract] [Full Text] [PDF]

				S. Zhang, P. Hemmerich, and F. Grosse Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2) J. Cell Sci., August 1, 2004; 117(17): 3935 - 3945. [Abstract] [Full Text] [PDF]