BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in C. elegans oocytes

Borja, Laura Bel; Soubigou, Flavie; Taylor, Samuel J P; Bringas, Conchita Fraguas; Budrewicz, Jacqueline; Lara-González, Pablo; Turpin, Christopher G Sorensen; Bembenek, Joshua N.; Cheerambathur, Dhanya K.; Pelisch, Federico

doi:10.7554/elife.65307

Cited by 17 publications

(17 citation statements)

References 81 publications

(101 reference statements)

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“…This pool does not depend on kinetochore localization, as shown by the sensitivity of Spc105R-RNAi (Wang et al, 2019) and BubR1-RNAi (this paper) oocyte spindles to BN2 treatment. This pool could be equivalent to the spindle-localized PP2A in C. elegans meiosis (Bel Borja et al, 2020).…”

Section: Pp2a-b56 Is Required To Maintain Meiotic Cohesionmentioning

confidence: 99%

Multiple pools of PP2A regulate spindle assembly, kinetochore attachments and cohesion in Drosophila oocytes

Jang

Gladstein

Das

et al. 2021

Journal of Cell Science

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Meiosis in female oocytes lacks centrosomes, the microtubule-organizing center. In Drosophila oocytes, meiotic spindle assembly depends on the chromosomal passenger complex (CPC). To investigate the mechanisms that regulate Aurora B activity, we examined the role of Protein Phosphatase 2A (PP2A) in oocyte meiosis. We found that both forms of PP2A, B55 and B56, antagonize the Aurora B spindle assembly function, suggesting that a balance between Aurora B and PP2A activity maintains the oocyte spindle during meiosis I. PP2A-B56, which is encoded by two partially redundant paralogs, wdb and wrd, is also required for maintaining sister chromatid cohesion, establishing end-on microtubule attachments, and the metaphase I arrest in oocytes. WDB recruitment to the centromeres depends on BUBR1, MEI-S332, and kinetochore protein SPC105R. While BUBR1 stabilizes microtubule attachments in Drosophila oocytes, it is not required for cohesion maintenance during meiosis I. We propose at least three populations of PP2A-B56 regulate meiosis, two of which depend on SPC105R and a third that is associated with the spindle.

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Section: Pp2a-b56 Is Required To Maintain Meiotic Cohesionmentioning

confidence: 99%

Multiple pools of PP2A regulate spindle assembly, kinetochore attachments and cohesion in Drosophila oocytes

Jang

Gladstein

Das

et al. 2021

Journal of Cell Science

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“…Interestingly in C. elegans Bub1 harbors a functional LxxIxE motif at position 282-287 C-terminal to the Bub3 binding site while in budding yeast the LxxIxE motif is present in Mad3 like human cells 28 . The fact that Bub1 in C. elegans contains a functional LxxIxE motif could suggest that dephosphorylation of T407, the interaction site for Mad1, is less efficiently dephosphorylated by the bound PP2A-B56 11, 38 . This would be in line with our data on Bub1 B56N that allows for a functional checkpoint as it does not affect phosphorylation of Bub1 T461.…”

Section: Resultsmentioning

confidence: 99%

“…S1C). However, human Bub1 also contains a putative PP2A-B56 binding motif (aa 654-FSPIQE-659) and Bub1 in C. elegans has been shown to bind directly to PP2A-B56 38 . We therefore first investigated if the PP2A-B56 binding motif in human Bub1 was functionally important.…”

Section: Chromosome Alignment Is Supported By Engineered Bub1 Protein...mentioning

confidence: 99%

Separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis

Nilsson

Wang

Kruse

et al. 2022

Preprint

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The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogues with Bub1 being a kinase while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1-PP2A-B56 complex can supports chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation resulting in reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment.

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“…PP2A regulates the cell cycle by affecting several critical pathways ( Wlodarchak and Xing, 2016 ) including Wnt, mammalian target of rapamycin (mTOR), mitogen activated protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K). PP2A-B56 is also involved in the regulation of spindle assembly ( Espert et al., 2014 ; Hayward et al., 2019 ), the cell cycle ( Janssens and Goris, 2001 ), apoptosis ( Janssens and Rebollo, 2012 ), DNA damage response ( Peng and Maller, 2010 ) and chromosome segregation during meiosis ( Bel Borja et al., 2020 ).…”

Section: Structure Function and Regulation Of Pp2amentioning

confidence: 99%

PP2A Phosphatase as an Emerging Viral Host Factor

Barski

Minnell

Maertens

2021

Front. Cell. Infect. Microbiol.

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Protein phosphatase 2A (PP2A) is one of the most ubiquitous cellular proteins and is responsible for the vast majority of Ser/Thr phosphatase activity in eukaryotes. PP2A is a heterotrimer, and its assembly, intracellular localization, enzymatic activity, and substrate specificity are subject to dynamic regulation. Each of its subunits can be targeted by viral proteins to hijack and modulate its activity and downstream signaling to the advantage of the virus. Binding to PP2A is known to be essential to the life cycle of many viruses and seems to play a particularly crucial role for oncogenic viruses, which utilize PP2A to transform infected cells through controlling the cell cycle and apoptosis. Here we summarise the latest developments in the field of PP2A viral targeting; in particular recent discoveries of PP2A hijacking through molecular mimicry of a B56-specific motif by several different viruses. We also discuss the potential as well as shortcomings for therapeutic intervention in the face of our current understanding of viral PP2A targeting.

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BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in C. elegans oocytes

Cited by 17 publications

References 81 publications

Multiple pools of PP2A regulate spindle assembly, kinetochore attachments and cohesion in Drosophila oocytes

Multiple pools of PP2A regulate spindle assembly, kinetochore attachments and cohesion in Drosophila oocytes

Separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis

PP2A Phosphatase as an Emerging Viral Host Factor

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