Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

Seo, Jae Sung; Kim, Hana; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Kyung Rim; Yoon, Hyun-Joo; Yoo, Hae Young; Choi, Cheol Yong

doi:10.1016/j.bbrc.2013.11.107

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…The binding of NuMA to a number of very different proteins, and its involvement in multiple major cellular functions (from mitotic spindle maintenance to several nuclear pathways for gene expression and DNA repair control) brings the issue of the regulation of these interactions. A number of reports have now demonstrated posttranslational modifications for NuMA, such as phosphorylation ( 60 – 66 ), glycosylation ( 67 ), sumoylation ( 68 ) and ubiquitination ( 69 ), some of which might account for the changing patterns of NuMA bands seen by electrophoresis (e.g. NuMA often appears as a doublet, as shown on several of our western blot images).…”

Section: Discussionsupporting

confidence: 55%

The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner

Jayaraman

Chittiboyina

Bai

et al. 2017

Nucleic Acids Research

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The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis.

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Section: Discussionsupporting

confidence: 55%

The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner

Jayaraman

Chittiboyina

Bai

et al. 2017

Nucleic Acids Research

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“…SUMOylation is involved in myriad cellular events 15 16 , SUMO-1 physically localizes to spindle in both mitotic and meiotic cells 19 53 . Not surprising, several microtubule-associated proteins are targets of SUMO-1, such as Aurora A, RanGAP1 and NuMA and this modification is required for their normal spindle localization and functions 16 27 53 . In contrast, SUMO-2/3 are more concentrated at centromeres, and thus, proteins located at centromeres and kinetochores are often modified by SUMO-2/3, including BubR1, Topoisomerase IIa and Aurora B 15 54 .…”

Section: Discussionmentioning

confidence: 99%

“…SUMOylation, one of the most dynamic post-translational modifications that exerts pivotal roles in dictating numerous cell-cycle events 15 16 and this modification can be reversed by SUMO-specific enzymes (SENPs) 17 . Mammals expresses six SENPs (SENP1-3 and SENP5-7) 18 , those of which are liberated to varieties of roles including cohesion maintenance, spindle assembly and embryonic development 19 20 21 22 .…”

mentioning

confidence: 99%

The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes

Huang

Khan

et al. 2015

Sci Rep

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Oocyte meiosis is a transcription quiescence process and the cell-cycle progression is coordinated by multiple post-translational modifications, including SUMOylation. SENP3 an important deSUMOylation protease has been intensively studied in ribosome biogenesis and oxidative stress. However, the roles of SENP3 in cell-cycle regulation remain enigmatic, particularly for oocyte meiotic maturation. Here, we found that SENP3 co-localized with spindles during oocyte meiosis and silencing of SENP3 severely compromised the M phase entry (germinal vesicle breakdown, GVBD) and first polar body extrusion (PBI). The failure in polar body extrusion was due to the dysfunction of γ-tubulin that caused defective spindle morphogenesis. SENP3 depletion led to mislocalization and a substantial loss of Aurora A (an essential protein for MTOCs localization and spindle dynamics) while irregularly dispersed distribution of Bora (a binding partner and activator of Aurora A) in cytoplasm instead of concentrating at spindles. The SUMO-2/3 but not SUMO-1 conjugates were globally decreased by SENP3 RNAi. Additionally, the spindle assembly checkpoint remained functional upon SENP3 RNAi. Our findings renew the picture of SENP3 function by exploring its role in meiosis resumption, spindle assembly and following polar body emission during mouse oocyte meiotic maturation, which is potentially due to its proteolytic activity that facilitate SUMO-2/3 maturation.

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“…Some proteins of the Ran pathways, which play critical roles in spindle organization during mitosis, are also targets of SUMOylation (Joseph et al, ; Silverman‐Gavrila and Wilde, ; Cesario and McKim, ). Nuclear mitotic‐apparatus protein (NuMA) has recently been reported to be modified by SUMO‐1, and SUMOylation is necessary for the NuMA‐mediated formation and maintenance of mitotic‐spindle poles (Seo et al, ). Previous work on oocyte meiosis has shown that NuMA and γ‐tubulin localize to the meiotic spindle poles and are important regulators of spindle organization (Lee et al, ).…”

Section: Discussionmentioning

confidence: 99%

SUMO‐1 plays crucial roles for spindle organization, chromosome congression, and chromosome segregation during mouse oocyte meiotic maturation

Yuan

Zhai

Liu

et al. 2014

Molecular Reproduction Devel

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Small ubiquitin-related modifier-1 (SUMO-1)-dependent modifications of many target proteins are involved in a range of intracellular processes. Previous studies reported the localization of SUMO-1 during oocyte meiosis, and that overexpression of Sentrin/SUMO-specific protease 2 (SENP2), a de-SUMOylation protease, altered SUMO-modified proteins, and caused defects in metaphase-II spindle organization. In this study, we detailed the consequences of SUMO-1-mediated SUMOylation by either inhibition of SUMO-1 or UBC9 with a specific antibody or their depletion by specific siRNA microinjection. Inhibition or depletion of SUMO-1 or UBC9 in germinal vesicle (GV)-stage oocytes decreased the rates of germinal vesicle breakdown and first polar body (PB1) extrusion; caused defective spindle organization and misaligned chromosomes; and led to aneuploidy in matured oocytes. Stage-specific antibody injections suggested that SUMO-1 functions before anaphase I during PB1 extrusion. Further experiments indicated that the localization of γ-tubulin was disordered after SUMO-1 inhibition, and that SUMO-1 depletion disrupted kinetochore-microtubule attachment at metaphase I. Moreover, SUMO-1 inhibition resulted in less-condensed chromosomes, altered localization of REC8 and securin, and reduced BUBR1 accumulation at the centromere. On the other hand, overexpression of SUMO-1 in GV-stage oocytes had no significant effect on oocyte maturation. In conclusion, our results implied that SUMO-1 plays crucial roles during oocyte meiotic maturation, specifically involving spindle assembly and chromosome behavior, by regulating kinetochore-microtubule attachment and the localization of γ-tubulin, BUBR1, REC8, and securin.

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Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

Cited by 9 publications

References 24 publications

The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner

The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner

The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes

SUMO‐1 plays crucial roles for spindle organization, chromosome congression, and chromosome segregation during mouse oocyte meiotic maturation

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