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V Sudakin, D Ganoth, A Dahan, H Heller, J Hershko, FC Luca, JV Ruderman and A Hershko
Unit of Biochemistry, B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
The ubiquitin-mediated degradation of mitotic cyclins is required for cells to exit from mitosis. Previous work with cell-free systems has revealed four components required for cyclin-ubiquitin ligation and proteolysis: a nonspecific ubiquitin-activating enzyme E1, a soluble fraction containing a ubiquitin carrier protein activity called E2-C, a crude particulate fraction containing a ubiquitin ligase (E3) activity that is activated during M-phase, and a constitutively active 26S proteasome that degrades ubiquitinated proteins. Here, we identify a novel approximately 1500-kDa complex, termed the cyclosome, which contains a cyclin-selective ubiquitin ligase activity, E3-C. E3-C is present but inactive during interphase; it can be activated in vitro by the addition of cdc2, enabling the transfer of ubiquitin from E2-C to cyclin. The kinetics of E3-C activation suggest the existence of one or more intermediates between cdc2 and E3-C. Cyclosome-associated E3-C acts on both cyclin A and B, and requires the presence of wild-type N- terminal destruction box motifs in each cyclin. Ubiquitinated cyclins are then rapidly recognized and degraded by the proteasome. These results identify the cyclosome-associated E3-C as the component of the cyclin destruction machinery whose activity is ultimately regulated by cdc2 and, as such, the element directly responsible for setting mitotic cyclin levels during early embryonic cell cycles.
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D. Perez-Mongiovi, C. Beckhelling, P. Chang, C. C. Ford, and E. Houliston Nuclei and Microtubule Asters Stimulate Maturation/M Phase Promoting Factor (Mpf) Activation in Xenopus Eggs and Egg Cytoplasmic Extracts J. Cell Biol., September 4, 2000; 150(5): 963 - 974. [Abstract] [Full Text] [PDF]
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A. Frankel, S. Man, P. Elliott, J. Adams, and R. S. Kerbel Lack of Multicellular Drug Resistance Observed in Human Ovarian and Prostate Carcinoma Treated with the Proteasome Inhibitor PS-341 Clin. Cancer Res., September 1, 2000; 6(9): 3719 - 3728. [Abstract] [Full Text]
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A. Yamanaka, S. Hatakeyama, K.-i. Kominami, M. Kitagawa, M. Matsumoto, and K.-i. Nakayama Cell Cycle-Dependent Expression of Mammalian E2-C Regulated by the Anaphase-Promoting Complex/Cyclosome Mol. Biol. Cell, August 1, 2000; 11(8): 2821 - 2831. [Abstract] [Full Text]
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J. L. Burton and M. J. Solomon Hsl1p, a Swe1p Inhibitor, Is Degraded via the Anaphase-Promoting Complex Mol. Cell. Biol., July 1, 2000; 20(13): 4614 - 4625. [Abstract] [Full Text] [PDF]
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J. D. Leverson, C. A.P. Joazeiro, A. M. Page, H.-k. Huang, P. Hieter, and T. Hunter The APC11 RING-H2 Finger Mediates E2-Dependent Ubiquitination Mol. Biol. Cell, July 1, 2000; 11(7): 2315 - 2325. [Abstract] [Full Text]
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A. D. Rudner, K. G. Hardwick, and A. W. Murray Cdc28 Activates Exit from Mitosis in Budding Yeast J. Cell Biol., June 26, 2000; 149(7): 1361 - 1376. [Abstract] [Full Text] [PDF]
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A. D. Rudner and A. W. Murray Phosphorylation by Cdc28 Activates the Cdc20-Dependent Activity of the Anaphase-Promoting Complex J. Cell Biol., June 26, 2000; 149(7): 1377 - 1390. [Abstract] [Full Text] [PDF]
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E. R. Kramer, N. Scheuringer, A. V. Podtelejnikov, M. Mann, and J.-M. Peters Mitotic Regulation of the APC Activator Proteins CDC20 and CDH1 Mol. Biol. Cell, May 1, 2000; 11(5): 1555 - 1569. [Abstract] [Full Text]
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A. Meimoun, T. Holtzman, Z. Weissman, H. J. McBride, D. J. Stillman, G. R. Fink, and D. Kornitzer Degradation of the Transcription Factor Gcn4 Requires the Kinase Pho85 and the SCFCDC4 Ubiquitin-Ligase Complex Mol. Biol. Cell, March 1, 2000; 11(3): 915 - 927. [Abstract] [Full Text]
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H. Yamada, S Matsumoto, and T Matsumoto High dosage expression of a zinc finger protein, Grt1, suppresses a mutant of fission yeast slp1(+), a homolog of CDC20/p55CDC/Fizzy J. Cell Sci., January 11, 2000; 113(22): 3989 - 3999. [Abstract] [PDF]
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K. C. Chen, A. Csikasz-Nagy, B. Gyorffy, J. Val, B. Novak, and J. J. Tyson Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle Mol. Biol. Cell, January 1, 2000; 11(1): 369 - 391. [Abstract] [Full Text]
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H. Bastians, L. M. Topper, G. L. Gorbsky, and J. V. Ruderman Cell Cycle-regulated Proteolysis of Mitotic Target Proteins Mol. Biol. Cell, November 1, 1999; 10(11): 3927 - 3941. [Abstract] [Full Text]
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T. P. Moynihan, H. C. Ardley, U. Nuber, S. A. Rose, P. F. Jones, A. F. Markham, M. Scheffner, and P. A. Robinson The Ubiquitin-conjugating Enzymes UbcH7 and UbcH8 Interact with RING Finger/IBR Motif-containing Domains of HHARI and H7-AP1 J. Biol. Chem., October 22, 1999; 274(43): 30963 - 30968. [Abstract] [Full Text] [PDF]
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E. Bailly and S. I. Reed Functional Characterization of Rpn3 Uncovers a Distinct 19S Proteasomal Subunit Requirement for Ubiquitin-Dependent Proteolysis of Cell Cycle Regulatory Proteins in Budding Yeast Mol. Cell. Biol., October 1, 1999; 19(10): 6872 - 6890. [Abstract] [Full Text] [PDF]
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C. Gieffers, B. H. Peters, E. R. Kramer, C. G. Dotti, and J.-M. Peters Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons PNAS, September 28, 1999; 96(20): 11317 - 11322. [Abstract] [Full Text] [PDF]
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G.K.T. Chan, S.A. Jablonski, V. Sudakin, J.C. Hittle, and T.J. Yen Human Bubr1 Is a Mitotic Checkpoint Kinase That Monitors Cenp-E Functions at Kinetochores and Binds the Cyclosome/APC J. Cell Biol., September 6, 1999; 146(5): 941 - 954. [Abstract] [Full Text] [PDF]
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R. A. Hastings, I. Eyheralde, S. P. Dawson, G. Walker, S. E. Reynolds, M. A. Billett, and R. J. Mayer A 220-kDa Activator Complex of the 26 S Proteasome in Insects and Humans. A ROLE IN TYPE II PROGRAMMED INSECT MUSCLE CELL DEATH AND CROSS-ACTIVATION OF PROTEASOMES FROM DIFFERENT SPECIES J. Biol. Chem., September 3, 1999; 274(36): 25691 - 25700. [Abstract] [Full Text] [PDF]
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S. Kotani, H. Tanaka, H. Yasuda, and K. Todokoro Regulation of APC Activity by Phosphorylation and Regulatory Factors J. Cell Biol., August 23, 1999; 146(4): 791 - 800. [Abstract] [Full Text] [PDF]
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W. Zachariae and K. Nasmyth Whose end is destruction: cell division and the anaphase-promoting complex Genes & Dev., August 15, 1999; 13(16): 2039 - 2058. [Full Text]
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P.-Y. Goh and U. Surana Cdc4, a Protein Required for the Onset of S Phase, Serves an Essential Function during G2/M Transition in Saccharomyces cerevisiae Mol. Cell. Biol., August 1, 1999; 19(8): 5512 - 5522. [Abstract] [Full Text] [PDF]
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R. L. Tinker-Kulberg and D. O. Morgan Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage Genes & Dev., August 1, 1999; 13(15): 1936 - 1949. [Abstract] [Full Text]
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O. Cohen-Fix and D. Koshland Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit Genes & Dev., August 1, 1999; 13(15): 1950 - 1959. [Abstract] [Full Text]
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R.-H. Chen, D. M. Brady, D. Smith, A. W. Murray, and K. G. Hardwick The Spindle Checkpoint of Budding Yeast Depends on a Tight Complex between the Mad1 and Mad2 Proteins Mol. Biol. Cell, August 1, 1999; 10(8): 2607 - 2618. [Abstract] [Full Text]
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G. Goshima, S. Saitoh, and M. Yanagida Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation Genes & Dev., July 1, 1999; 13(13): 1664 - 1677. [Abstract] [Full Text]
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D. C. Farruggio, F. M. Townsley, and J. V. Ruderman Cdc20 associates with the kinase aurora2/Aik PNAS, June 22, 1999; 96(13): 7306 - 7311. [Abstract] [Full Text] [PDF]
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L. Cheng, T. Collyer, and C. F. J. Hardy Cell Cycle Regulation of DNA Replication Initiator Factor Dbf4p Mol. Cell. Biol., June 1, 1999; 19(6): 4270 - 4278. [Abstract] [Full Text] [PDF]
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K. G. Hardwick, R. Li, C. Mistrot, R.-H. Chen, P. Dann, A. Rudner, and A. W. Murray Lesions in Many Different Spindle Components Activate the Spindle Checkpoint in the Budding Yeast Saccharomyces cerevisiae Genetics, June 1, 1999; 152(2): 509 - 518. [Abstract] [Full Text]
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R. Fraschini, E. Formenti, G. Lucchini, and S. Piatti Budding Yeast Bub2 Is Localized at Spindle Pole Bodies and Activates the Mitotic Checkpoint via a Different Pathway from Mad2 J. Cell Biol., May 31, 1999; 145(5): 979 - 991. [Abstract] [Full Text] [PDF]
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