Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A
Open accessAbstract
Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
RSK2-mediated phosphorylation of Emi2 promotes its interaction with PP2A-B56.
“it was recently reported that RSK2-mediated phosphorylation of Emi2 promotes its well-known interaction with PP2A-B5652,53.”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [52]
The Results (page not provided) report that Mos promotes Emi2–PP2A binding through Rsk and that mutating Rsk phosphorylation sites abolishes the enhanced interaction. The paper identifies the binding partner as PP2A, not specifically PP2A-B56, so it does not support that subunit-level detail. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes
Masui, Y., & Markert, C. L. (1971) · Journal of Experimental Zoology · doi:10.1002/jez.1401770202 · Cited by 1,559 · see citing works
Sagata, N., Watanabe, N., Woude, G. F. V., & Ikawa, Y. (1989) · Nature · doi:10.1038/342512a0 · Cited by 642 · see citing works
Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase
Haccard, O., Sarcevic, B., Lewellyn, A. L., Hartley, R., Roy, L. M., Izumi, T., ERIKSON, E., & Maller, J. L. (1993) · Science · doi:10.1126/science.8235656 · Cited by 261 · see citing works
Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation
Rauh, N. R., Schmidt, A., Bormann, J., Nigg, E. A., & Mayer, T. U. (2005) · Nature · doi:10.1038/nature04093 · Cited by 228 · see citing works
Hansen, D. V., Loktev, A. V., Ban, K. H.-K., & Jackson, P. K. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-07-0598 · Cited by 210 · see citing works
Self-citationXenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activityPreprint
Schmidt, A., Duncan, P. I., Rauh, N. R., Sauer, G., Fry, A. M., Nigg, E. A., & Mayer, T. U. (2005) · Genes & Development · doi:10.1101/gad.320705 · Cited by 193 · see citing works
Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20
Shoji, S., Yoshida, N., Amanai, M., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600953 · Cited by 189 · see citing works
Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis
Madgwick, S., Hansen, D. V., Levasseur, M., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200604140 · Cited by 181 · see citing works
Self-citationTung, J. J., Hansen, D. V., Ban, K. H.-K., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501108102 · Cited by 175 · see citing works
Self-citationThe Protein Kinase p90 Rsk as an Essential Mediator of Cytostatic Factor Activity
Bhatt, R. R., & Ferrell, J. E. (1999) · Science · doi:10.1126/science.286.5443.1362 · Cited by 165 · see citing works
Liu, J., & Maller, J. L. (2005) · Current Biology · doi:10.1016/j.cub.2005.07.030 · Cited by 158 · see citing works
Induction of Metaphase Arrest in Cleaving Xenopus Embryos by the Protein Kinase p90 Rsk
Gross, S. D., Schwab, M. S., Lewellyn, A. L., & Maller, J. L. (1999) · Science · doi:10.1126/science.286.5443.1365 · Cited by 146 · see citing works
Hansen, D. V., Tung, J. J., & Jackson, P. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509549102 · Cited by 146 · see citing works
Self-citationA direct link of the Mos–MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs
Inoue, D., Ohe, M., Kanemori, Y., Nobui, T., & Sagata, N. (2007) · Nature · doi:10.1038/nature05688 · Cited by 135 · see citing works
Emi1 is required for cytostatic factor arrest in vertebrate eggs
Reimann, J. D. R., & Jackson, P. K. (2002) · Nature · doi:10.1038/416850a · Cited by 120 · see citing works
Self-citationPhosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs
Nishiyama, T., Ohsumi, K., & Kishimoto, T. (2007) · Nature · doi:10.1038/nature05696 · Cited by 118 · see citing works
Phillips, K. P., Petrunewich, M. A. F., Collins, J. L., et al. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0680 · Cited by 104 · see citing works
Tunquist, B. J., Schwab, M. S., Chen, L. G., et al. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00894-1 · Cited by 95 · see citing works
Requirement for MAPK Activation for Normal Mitotic Progression in Xenopus Egg Extracts
Guadagno, T. M., & Ferrell, J. E. (1998) · Science · doi:10.1126/science.282.5392.1312 · Cited by 93 · see citing works
Regulation of the Cyclin B Degradation System by an Inhibitor of Mitotic Proteolysis
Vorlaufer, E., & Peters, J. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.7.1817 · Cited by 64 · see citing works
Erp1/Emi2 is essential for the meiosis I to meiosis II transition in Xenopus oocytes
Ohe, M., Inoue, D., Kanemori, Y., et al. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.10.044 · Cited by 58 · see citing works
Activation of Wee1 by p42 MAPK In Vitro and in CyclingXenopusEgg Extracts
Walter, S. A., Guadagno, S. N., & Ferrell, J. E. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.3.887 · Cited by 58 · see citing works
Liu, J., Grimison, B., Lewellyn, A. L., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606607200 · Cited by 57 · see citing works
A Role for Cdc2- and PP2A-Mediated Regulation of Emi2 in the Maintenance of CSF Arrest
Wu, Q., Guo, Y., Yamada, A., et al. (2007) · Current Biology · doi:10.1016/j.cub.2006.12.045 · Cited by 53 · see citing works
Self-citationAPC/C–Cdc20-mediated degradation of cyclin B participates in CSF arrest in unfertilized Xenopus eggs
Yamamoto, T. M., Iwabuchi, M., Ohsumi, K., et al. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.12.025 · Cited by 49 · see citing works
Translational Unmasking of Emi2 Directs Cytostatic Factor Arrest in Meiosis II
Tung, J. J., Padmanabhan, K., Hansen, D. V., et al. (2007) · Cell Cycle · doi:10.4161/cc.6.6.3936 · Cited by 36 · see citing works
Self-citationInhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase
Casaletto, J. B., Nutt, L. K., Wu, Q., Moore, J. D., Etkin, L. D., Jackson, P. K., Hunt, T., & Kornbluth, S. A. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200411056 · Cited by 23 · see citing works
Self-citationEmi2 at the Crossroads: Where CSF Meets MPF
Hansen, D. V., Pomerening, J. R., Summers, M. K., et al. (2007) · Cell Cycle · doi:10.4161/cc.6.6.3937 · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases
Cargnello, M., & Roux, P. P. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00031-10 · Cited by 3,274 · see citing works
A Conserved Motif Provides Binding Specificity to the PP2A-B56 Phosphatase
Hertz, E. P. T., Kruse, T., Davey, N. E., López-Méndez, B., Sigurðsson, J. O., Montoya, G., Olsen, J. V., & Nilsson, J. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.06.024 · Cited by 282 · see citing works
Isoda, M., Sako, K., Suzuki, K., Nishino, K., Nakajo, N., Ohe, M., Ezaki, T., Kanemori, Y., Inoue, D., Ueno, H., et al. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.029 · Cited by 42 · see citing works
Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A
Pavic, K., Gupta, N., Omella, J. D., Derua, R., Aakula, A., Huhtaniemi, R., Määttä, J. A., Höfflin, N., Okkeri, J., Wang, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36693-9 · Cited by 36 · see citing works
“The data show that the CIP2A(1-560) residues cross-linked to B56α are located primarily in the N-terminal head domain (K18, K21, E23, E34, K40) with an additional residue at the C-terminus (K490) (Fig.”
BackgroundMethodInfluential
- Authors
- Wu, J. Q., Hansen, D. V., Guo, Y., Wang, M. Z., Tang, W., Freel, C. D., Tung, J. J., Jackson, P. K., & Kornbluth, S.
- Affiliations
- Duke University (US)
- Genentech (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-10-16
- Volume
- 104
- Issue
- 42
- Pages
- 16564-16569
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2034268
- OpenAlex
- W2066730352
- Cited by
- 56
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- UNC Libraries
- Funders
- National Institute of General Medical Sciences (R01GM067225, R01GM073023)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- Emi2, protein phosphatase 2A, MOS, anaphase-promoting complex, cytostatic factor, meiotic arrest, protein stability, Cdc2 phosphorylation, protein-protein interaction
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Meiosis, Molecular Sequence Data, Ovum, Phosphorylase Phosphatase, Phosphorylation, Xenopus, Signal Transduction, Proto-Oncogene Proteins c-mos, Ribosomal Protein S6 Kinases, Xenopus Proteins, F-Box Proteins
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
