A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis
Open accessPublished version of a preprint
Abstract
The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A-B56 phosphatase through a coiled-coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A-B56-hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A-B56 substrates containing a canonical B56 binding motif. We find that PP2A-B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 1× · see citing works
“Quantification of LC-MS/MS spectra was performed using BasicQuan or MassChroQ (Valot et al, 2011) and the iBAQ method (Schwanhausser et al, 2011).”
Structure of the Protein Phosphatase 2A Holoenzyme
Xu, Y., Xing, Y., Chen, Y., Chao, Y., Lin, Z., Fan, E., Yu, J. W., Strack, S., Jeffrey, P. D., & Shi, Y. (2006) · Cell · doi:10.1016/j.cell.2006.11.033 · Cited by 450 · see citing works
Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion
Hara, K., Zheng, G., Qu, Q., Liu, H., Ouyang, Z., Chen, Z., Tomchick, D. R., & Yu, H. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2880 · Cited by 166 · see citing works
Expanding the PP2A Interactome by Defining a B56-Specific SLiM
Wang, X., Bajaj, R., Bollen, M., Peti, W., & Page, R. (2016) · Structure · doi:10.1016/j.str.2016.09.010 · Cited by 149 · see citing works
A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment
Wang, X., Garvanska, D. H., Nasa, I., Ueki, Y., Zhang, G., Kettenbach, A. N., Peti, W., Nilsson, J., & Page, R. (2020) · eLife · doi:10.7554/elife.55966 · Cited by 53 · see citing works
Self-citation
Flagged first, then by citations
- Authors
- Ueki, Y., Hadders, M. A., Weisser, M. B., Nasa, I., Sotelo-Parrilla, P., Cressey, L. E., Gupta, T., Hertz, E. P. T., Kruse, T., Montoya, G., Jeyaprakash, A. A., Kettenbach, A., Lens, S. M. A., & Nilsson, J.
- Affiliations
- University of Copenhagen (DK)
- Utrecht University (NL)
- Dartmouth College (US)
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Nilsson, Jakob
- ORCID
- Venue
- The EMBO Reports
- Published
- 2021-05-11
- Volume
- 22
- Issue
- 7
- Pages
- e52295-e52295
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC8256288
- OpenAlex
- W3161253920
- Cited by
- 16
- References
- 5
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- EMBO Reports (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Novo Nordisk Fonden (NNF14CC0001, NNF0024386, NNF18OC0053124, NNF17SA0030214)
- Danish Cancer Society Research Center (R167- A10951-17-S2)
- Independent Research Fund Denmark (8021-00101B)
- Swiss National Fund (P2EZP3_178624)
- Lundbeckfonden (2017-3212)
- HHS|NIH|National Institute of General Medical Sciences (R35GM119455)
- NIH (S10-OD016212)
- Dutch Cancer Society (KWF research project 10366)
- Wellcome Trust (095822, 202811202811)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- mitosis
- MeSH terms
- Centromere, Humans, Meiosis, Mitosis, CDC2 Protein Kinase, Cell Cycle Proteins, Protein Phosphatase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
