SUMO-2/3 Modification and Binding Regulate the Association of CENP-E with Kinetochores and Progression through Mitosis

Xiang Dong Zhang; Jacqueline Goeres; Hong Zhang; Tim J. Yen; Andrew C.G. Porter; Michael J. Matunis

doi:10.1016/j.molcel.2008.01.013

SUMO-2/3 Modification and Binding Regulate the Association of CENP-E with Kinetochores and Progression through Mitosis

Xiang Dong Zhang, Jacqueline Goeres, Hong Zhang, Tim J. Yen, Andrew C.G. Porter, Michael J. Matunis

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

180 Scopus citations

Abstract

SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.

Original language	English (US)
Pages (from-to)	729-741
Number of pages	13
Journal	Molecular cell
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2008.01.013
State	Published - Mar 28 2008

Keywords

CELLCYCLE
PROTEINS

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2008.01.013

Cite this

@article{10b78b86872f4246b0a6690b31fa1fd8,

title = "SUMO-2/3 Modification and Binding Regulate the Association of CENP-E with Kinetochores and Progression through Mitosis",

abstract = "SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.",

keywords = "CELLCYCLE, PROTEINS",

author = "Zhang, {Xiang Dong} and Jacqueline Goeres and Hong Zhang and Yen, {Tim J.} and Porter, {Andrew C.G.} and Matunis, {Michael J.}",

note = "Funding Information: We thank Drs. Don Cleveland, Ann Pluta, Ted Salmon, Yixian Zheng, William Brinkley, and Paul Freemont for antibodies. We also thank members of the Matunis laboratory and Drs. Mary Dasso and Robert Cohen for insightful discussions. This work was supported by a grant from the National Institutes of Health (GM060980 to M.J.M.) and the Lang Fellowship Fund (X.-D.Z.). ",

year = "2008",

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doi = "10.1016/j.molcel.2008.01.013",

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T1 - SUMO-2/3 Modification and Binding Regulate the Association of CENP-E with Kinetochores and Progression through Mitosis

AU - Zhang, Xiang Dong

AU - Goeres, Jacqueline

AU - Zhang, Hong

AU - Yen, Tim J.

AU - Porter, Andrew C.G.

AU - Matunis, Michael J.

N1 - Funding Information: We thank Drs. Don Cleveland, Ann Pluta, Ted Salmon, Yixian Zheng, William Brinkley, and Paul Freemont for antibodies. We also thank members of the Matunis laboratory and Drs. Mary Dasso and Robert Cohen for insightful discussions. This work was supported by a grant from the National Institutes of Health (GM060980 to M.J.M.) and the Lang Fellowship Fund (X.-D.Z.).

PY - 2008/3/28

Y1 - 2008/3/28

N2 - SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.

AB - SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.

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