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The E2-C Vihar Is Required for the Correct Spatiotemporal Proteolysis of Cyclin B and Itself Undergoes Cyclical Degradation

Máthé, Endre and Kraft, Claudine and Giet, Régis and Deák, Péter and Peters, Jan-Michael and Glover, David M. (2004) The E2-C Vihar Is Required for the Correct Spatiotemporal Proteolysis of Cyclin B and Itself Undergoes Cyclical Degradation. Current Biology, 14 (19). pp. 1723-1733. ISSN 0960-9822. doi:10.1016/j.cub.2004.09.023.

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Background: Proteolytic degradation of mitotic regulatory proteins first requires these targets to be ubiquitinated. This is regulated at the level of conjugation of ubiquitin to substrates by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin-protein ligase. Substrate specificity and temporal activity of the APC/C has been thought to lie primarily with its two activators, Cdc20/Fizzy and Cdh1/Fizzy-related. Results: Here, we show that reduction in the E2 ubiquitin-conjugating enzyme (UBC) of the E2-C family that is encoded by the Drosophila gene vihar (vih), by either mutation or RNAi, leads to an accumulation of cells in a metaphase-like state. Cyclin B accumulates to high levels in all mitotic vih cells, particularly at the spindle poles. Vihar E2-C is present in the cytoplasm of mitotic cells but also associates with centrosomes, and its own degradation is initiated at the metaphase-anaphase transition. Expression of destruction D box mutants of vihar in the syncytial embryo results in mitotic arrest at late anaphase. In contrast to hypomorphic mutants, Cyclin B is degraded at the spindle poles and accumulates in the equatorial region of the spindle. Conclusions: In Drosophila, the Vihar E2 UBC contributes to the spatiotemporal control of Cyclin B degradation that first occurs at the spindle poles. APC/C-mediated proteolysis of Vihar E2-C autoinactivates the APC/C at the centrosome before a second wave of proteolysis to degrade Cyclin B on the rest of the spindle and elsewhere in the cell.

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Glover, David M.0000-0003-0956-0103
Additional Information:© 2004 Elsevier. Received 17 May 2004, Revised 8 July 2004, Accepted 2 August 2004, Available online 4 October 2004. We would like to thank Hiroyuki Ohkura for his contribution to some of the early screens of P element mutant collections; Adelaide T. Carpenter for isolating vihar-specific chromosomal rearrangements; and Matthew Savoian and Marisa Segal for stimulating discussions. We are also grateful for Justen Andrews, Brian Oliver, and David Huen for the Drosophila testis and embryonic cDNA libraries. Anti-BubR1 antibodies were kindly provided by Claudio Sunkel. We thank Mark Jackman and Jonathan Pines for their great help in FACS analysis with S2 cells. D.M.G. wishes to thank Cancer Research UK, and J.-M.P. wishes to thank Boehringer Ingleheim for support. Accession Numbers: The full-length vih cDNA sequence was submitted to GenBank on August 15, 2001 and was allocated the accession number AF410850.
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Issue or Number:19
Record Number:CaltechAUTHORS:20200806-163116265
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Official Citation:Endre Máthé, Claudine Kraft, Régis Giet, Péter Deák, Jan-Michael Peters, David M. Glover, The E2-C Vihar Is Required for the Correct Spatiotemporal Proteolysis of Cyclin B and Itself Undergoes Cyclical Degradation, Current Biology, Volume 14, Issue 19, 2004, Pages 1723-1733, ISSN 0960-9822,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104794
Deposited By: George Porter
Deposited On:10 Aug 2020 17:26
Last Modified:16 Nov 2021 18:35

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