Mad2 Transiently Associates with an APC/p55Cdc Complex During Mitosis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1998 Sep 16

PMID 9736712

Citations 39

Authors

K Wassmann

R Benezra

Affiliations

Soon will be listed here.

Abstract

Activation of the mitotic checkpoint pathway in response to mitotic spindle damage in eukaryotic cells delays the exit from mitosis in an attempt to prevent chromosome missegregation. One component of this pathway, hsMad2, has been shown in mammalian cells to physically associate with components of a ubiquitin ligase activity (termed the anaphase promoting complex or APC) when the checkpoint is activated, thereby preventing the degradation of inhibitors of the mitotic exit machinery. In the present report, we demonstrate that the inhibitory association between Mad2 and the APC component Cdc27 also takes place transiently during the early stages of a normal mitosis and is lost before mitotic exit. We also show that Mad2 associates with the APC regulatory protein p55Cdc in mammalian cells as has been reported in yeast. In contrast, however, this complex is present only in nocodazole-arrested or early mitotic cells and is associated with the APC as a Mad2/p55Cdc/Cdc27 ternary complex. Evidence for a Mad2/Cdc27 complex that forms independent of p55Cdc also is presented. These results suggest a model for the regulation of the APC by Mad2 and may explain how the spindle assembly checkpoint apparatus controls the timing of mitosis under normal growth conditions.

Citing Articles

FRET-FLIM for the Study of Protein-Protein Interactions Underpinning Mitosis Checkpoints.

Pain C Methods Mol Biol. 2024; 2874:87-97.

PMID: 39614049 DOI: 10.1007/978-1-0716-4236-8_8.

The importance of CDC27 in cancer: molecular pathology and clinical aspects.

Kazemi-Sefat G, Keramatipour M, Talebi S, Kavousi K, Sajed R, Kazemi-Sefat N Cancer Cell Int. 2021; 21(1):160.

PMID: 33750395 PMC: 7941923. DOI: 10.1186/s12935-021-01860-9.

Cyclin B3 promotes anaphase I onset in oocyte meiosis.

Karasu M, Bouftas N, Keeney S, Wassmann K J Cell Biol. 2019; 218(4):1265-1281.

PMID: 30723090 PMC: 6446836. DOI: 10.1083/jcb.201808091.

Rev7/Mad2B plays a critical role in the assembly of a functional mitotic spindle.

Bhat A, Wu Z, Maher V, McCormick J, Xiao W Cell Cycle. 2015; 14(24):3929-38.

PMID: 26697843 PMC: 4825701. DOI: 10.1080/15384101.2015.1120922.

How oocytes try to get it right: spindle checkpoint control in meiosis.

Touati S, Wassmann K Chromosoma. 2015; 125(2):321-35.

PMID: 26255654 DOI: 10.1007/s00412-015-0536-7.

References

Nusse M, Beisker W, Hoffmann C, Tarnok A . Flow cytometric analysis of G1- and G2/M-phase subpopulations in mammalian cell nuclei using side scatter and DNA content measurements. Cytometry. 1990; 11(7):813-21. DOI: 10.1002/cyto.990110707. View

Jorgensen P, Brundell E, Starborg M, Hoog C . A subunit of the anaphase-promoting complex is a centromere-associated protein in mammalian cells. Mol Cell Biol. 1998; 18(1):468-76. PMC: 121516. DOI: 10.1128/MCB.18.1.468. View

Li R, Murray A . Feedback control of mitosis in budding yeast. Cell. 1991; 66(3):519-31. DOI: 10.1016/0092-8674(81)90015-5. View

Giaretti W, Nusse M . Light scatter of isolated cell nuclei as a parameter discriminating the cell-cycle subcompartments. Methods Cell Biol. 1994; 41:389-400. DOI: 10.1016/s0091-679x(08)61730-6. View

Tugendreich S, Tomkiel J, Earnshaw W, Hieter P . CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition. Cell. 1995; 81(2):261-8. DOI: 10.1016/0092-8674(95)90336-4. View

King R, Peters J, Tugendreich S, Rolfe M, Hieter P, Kirschner M . A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell. 1995; 81(2):279-88. DOI: 10.1016/0092-8674(95)90338-0. View

Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca F . The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell. 1995; 6(2):185-97. PMC: 275828. DOI: 10.1091/mbc.6.2.185. View

Lahav-Baratz S, Sudakin V, Ruderman J, Hershko A . Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. Proc Natl Acad Sci U S A. 1995; 92(20):9303-7. PMC: 40973. DOI: 10.1073/pnas.92.20.9303. View

Hardwick K, Murray A . Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast. J Cell Biol. 1995; 131(3):709-20. PMC: 2120625. DOI: 10.1083/jcb.131.3.709. View

10.

Weiss E, Winey M . The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint. J Cell Biol. 1996; 132(1-2):111-23. PMC: 2120695. DOI: 10.1083/jcb.132.1.111. View

11.

Yamamoto A, Guacci V, Koshland D . Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s). J Cell Biol. 1996; 133(1):99-110. PMC: 2120772. DOI: 10.1083/jcb.133.1.99. View

12.

Hwang L, Lau L, Smith D, Mistrot C, Hardwick K, Hwang E . Budding yeast Cdc20: a target of the spindle checkpoint. Science. 1998; 279(5353):1041-4. DOI: 10.1126/science.279.5353.1041. View

13.

Kim S, Lin D, Matsumoto S, Kitazono A, Matsumoto T . Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science. 1998; 279(5353):1045-7. DOI: 10.1126/science.279.5353.1045. View

14.

Shirayama M, Zachariae W, Ciosk R, Nasmyth K . The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae. EMBO J. 1998; 17(5):1336-49. PMC: 1170482. DOI: 10.1093/emboj/17.5.1336. View

15.

Cahill D, Lengauer C, Yu J, Riggins G, WILLSON J, Markowitz S . Mutations of mitotic checkpoint genes in human cancers. Nature. 1998; 392(6673):300-3. DOI: 10.1038/32688. View

16.

Jin D, Spencer F, Jeang K . Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell. 1998; 93(1):81-91. DOI: 10.1016/s0092-8674(00)81148-4. View

17.

Farr K, Hoyt M . Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint. Mol Cell Biol. 1998; 18(5):2738-47. PMC: 110653. DOI: 10.1128/MCB.18.5.2738. View

18.

Waters J, Chen R, Murray A, Salmon E . Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol. 1998; 141(5):1181-91. PMC: 2137189. DOI: 10.1083/jcb.141.5.1181. View

19.

Gorbsky G, Chen R, Murray A . Microinjection of antibody to Mad2 protein into mammalian cells in mitosis induces premature anaphase. J Cell Biol. 1998; 141(5):1193-205. PMC: 2137176. DOI: 10.1083/jcb.141.5.1193. View

20.

Kallio M, Weinstein J, Daum J, Burke D, Gorbsky G . Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. J Cell Biol. 1998; 141(6):1393-406. PMC: 2132789. DOI: 10.1083/jcb.141.6.1393. View