title: Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA).
abstract: Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sun-Jick
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Bang
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ki Sa
authors.initials: KS
authors.lastname: Sung
authors.affiliation: TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850, USA.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710, Republic of Korea.
authors.forename: Hae Yong
authors.initials: HY
authors.lastname: Yoo
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: choicy@skku.ac.kr.
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D058207:Sumoylation; D020798:Two-Hybrid System Techniques
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D025842:SUMO-1 Protein; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases
keywords: Multiple spindle poles; NuMA; SENP1; Small ubiquitin-like modifier-1