QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Thornton, B. R. Articles by Toczyski, D. P. Search for Related Content PubMed PubMed Citation Articles by Thornton, B. R. Articles by Toczyski, D. P. Social Bookmarking                   What's this?

RESEARCH PAPER

An architectural map of the anaphase-promoting complex

¹ Cancer Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94115, USA; ² Department of Physiology, University of California, San Francisco, California 94143-2200, USA

The anaphase-promoting complex or cyclosome (APC) is an unusually complicated ubiquitin ligase, composed of 13 core subunits and either of two loosely associated regulatory subunits, Cdc20 and Cdh1. We analyzed the architecture of the APC using a recently constructed budding yeast strain that is viable in the absence of normally essential APC subunits. We found that the largest subunit, Apc1, serves as a scaffold that associates independently with two separable subcomplexes, one that contains Apc2 (Cullin), Apc11 (RING), and Doc1/Apc10, and another that contains the three TPR subunits (Cdc27, Cdc16, and Cdc23). We found that the three TPR subunits display a sequential binding dependency, with Cdc27 the most peripheral, Cdc23 the most internal, and Cdc16 between. Apc4, Apc5, Cdc23, and Apc1 associate interdependently, such that loss of any one subunit greatly reduces binding between the remaining three. Intriguingly, the cullin and TPR subunits both contribute to the binding of Cdh1 to the APC. Enzymatic assays performed with APC purified from strains lacking each of the essential subunits revealed that only cdc27 complexes retain detectable activity in the presence of Cdh1. This residual activity depends on the C-box domain of Cdh1, but not on the C-terminal IR domain, suggesting that the C-box mediates a productive interaction with an APC subunit other than Cdc27. We have also found that the IR domain of Cdc20 is dispensable for viability, suggesting that Cdc20 can activate the APC through another domain. We have provided an updated model for the subunit architecture of the APC.

[Keywords: APC; yeast; cullin; TPR; Cdh1; Cdc20]

Received November 30, 2005; revised version accepted December 22, 2005.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1396906.

³ These authors contributed equally to this work.

⁴ Corresponding author.

E-MAIL toczyski{at}cc.ucsf.edu; FAX (415) 502-3179.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Kimata, A. Matsuyama, K. Nagao, K. Furuya, C. Obuse, M. Yoshida, and M. Yanagida Diminishing HDACs by drugs or mutations promotes normal or abnormal sister chromatid separation by affecting APC/C and adherin J. Cell Sci., April 1, 2008; 121(7): 1107 - 1118. [Abstract] [Full Text] [PDF]

				K. Tran, J. A. Mahr, J. Choi, J. G. Teodoro, M. R. Green, and D. H. Spector Accumulation of Substrates of the Anaphase-Promoting Complex (APC) during Human Cytomegalovirus Infection Is Associated with the Phosphorylation of Cdh1 and the Dissociation and Relocalization of APC Subunits J. Virol., January 1, 2008; 82(1): 529 - 537. [Abstract] [Full Text] [PDF]

				M. Pal, O. Nagy, D. Menesi, A. Udvardy, and P. Deak Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster J. Cell Sci., September 15, 2007; 120(18): 3238 - 3248. [Abstract] [Full Text] [PDF]

				B. R. Thornton and D. P. Toczyski Precise destruction: an emerging picture of the APC. Genes & Dev., November 15, 2006; 20(22): 3069 - 3078. [Abstract] [Full Text] [PDF]

				H.-J. Yoon, A. Feoktistova, J.-S. Chen, J. L. Jennings, A. J. Link, and K. L. Gould Role of Hcn1 and Its Phosphorylation in Fission Yeast Anaphase-promoting Complex/Cyclosome Function J. Biol. Chem., October 27, 2006; 281(43): 32284 - 32293. [Abstract] [Full Text] [PDF]

				C. Acquaviva and J. Pines The anaphase-promoting complex/cyclosome: APC/C J. Cell Sci., June 15, 2006; 119(12): 2401 - 2404. [Full Text] [PDF]