Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cells
Open accessAbstract
Protein phosphatase 2A (PP2A) is a multifunctional phosphatase that plays important roles in many cellular processes including regulation of cell cycle and apoptosis. Because PP2A is involved in so many diverse processes, it is highly regulated by both non-covalent and covalent mechanisms that are still being defined. In this study we have investigated the importance of leucine carboxyl methyltransferase-1 (LCMT-1) for PP2A methylation and cell function. We show that reduction of LCMT-1 protein levels by small hairpin RNAs causes up to a 70% reduction in PP2A methylation in HeLa cells, indicating that LCMT-1 is the major mammalian PP2A methyltransferase. In addition, LCMT-1 knockdown reduced the formation of PP2A heterotrimers containing the Balpha regulatory subunit and, in a subset of the cells, induced apoptosis, characterized by caspase activation, nuclear condensation/fragmentation, and membrane blebbing. Knockdown of the PP2A Balpha regulatory subunit induced a similar amount of apoptosis, suggesting that LCMT-1 induces apoptosis in part by disrupting the formation of PP2A(BalphaAC) heterotrimers. Treatment with a pan-caspase inhibitor partially rescued cells from apoptosis induced by LCMT-1 or Balpha knockdown. LCMT-1 knockdown cells and Balpha knockdown cells were more sensitive to the spindle-targeting drug nocodazole, suggesting that LCMT-1 and Balpha are important for spindle checkpoint. Treatment of LCMT-1 and Balpha knockdown cells with thymidine dramatically reduced cell death, presumably by blocking progression through mitosis. Consistent with these results, homozygous gene trap knock-out of LCMT-1 in mice resulted in embryonic lethality. Collectively, our results indicate that LCMT-1 is important for normal progression through mitosis and cell survival and is essential for embryonic development in mice.
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?
A rather similar phenotype was observed in Lcmt1 knockout mice lacking detectable LCMT-1, which is predicted to majorly affect PP2A holoenzyme formation with B55 subunits.
“Interestingly, a rather similar phenotype was observed in Lcmt1 KO mice, lacking any detectable expression of the PP2A methyltransferase LCMT-1, which is predicted to majorly affect PP2A holoenzyme formation with B55 subunits [26,[39][40][41].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
Constitutive Lcmt1 knockout is embryonically lethal, and constitutive Ppme1 knockout is perinatally lethal at P1 due to inability to start normal breathing or suckling.
“constitutive KO of Lcmt1 was embryonically lethal, and constitutive KO of Ppme1 resulted in perinatal lethality, with all mice dying at P1 due to lack of ability to start normal breathing or suckling [39,56].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
At E12.5, Lcmt1 gt/gt embryos have misshapen eyes.
“-At E12.5: reduced embryo and liver weight; fetal liver hematopoiesis | defect (all lineages affected); misshapen eyes; indentation of the back | of the head”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
At E12.5, Lcmt1 gt/gt embryos have a fetal liver hematopoiesis defect affecting all lineages.
“-At E12.5: reduced embryo and liver weight; fetal liver hematopoiesis | defect (all lineages affected); misshapen eyes; indentation of the back | of the head”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
In mice with a gene-trap insertion in the first intron of Lcmt1 (German Gene Trap consortium clone), embryonic lethality occurs between E14.5 and E16.5, with 5% dying before E12.5.
“-Embryonic lethality between E14.5 and E16.5 (5% die before E12.5) [26,39,41]”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
At E12.5, Lcmt1 gt/gt embryos have an indentation of the back of the head.
“-At E12.5: reduced embryo and liver weight; fetal liver hematopoiesis | defect (all lineages affected); misshapen eyes; indentation of the back | of the head”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
In Lcmt1 -/- E14.5 MEFs, methylation of PP2A, PP4 and PP6 is decreased.
“-In -/-E14.5 MEFs: decreased methylation of PP2A, PP4 and PP6; | selective defects in PP2A-B55 and PP4-PPP4R1 complex formation”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
In Lcmt1 -/- E14.5 MEFs, formation of PP2A-B55 and PP4-PPP4R1 complexes is selectively defective.
“-In -/-E14.5 MEFs: decreased methylation of PP2A, PP4 and PP6; | selective defects in PP2A-B55 and PP4-PPP4R1 complex formation”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
At E12.5, Lcmt1 gt/gt embryos have reduced embryo and liver weight.
“-At E12.5: reduced embryo and liver weight; fetal liver hematopoiesis | defect (all lineages affected); misshapen eyes; indentation of the back | of the head”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [39]
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
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673 · see citing works
Staurosporine, a potent inhibitor of phospholipidCa++dependent protein kinase
Tamaoki, T., Nomoto, H., TAKAHASHI, I., Kato, Y., Morimoto, M., & Tomita, F. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)90008-2 · Cited by 2,452 · see citing works
Janssens, V., & Goris, J. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3530417 · Cited by 1,890 · see citing works
A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,803 · see citing works
Janssens, V., & Goris, J. (2001) · Biochemical Journal · doi:10.1042/bj3530417 · Cited by 1,392 · see citing works
Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I
Coleman, M. L., Sahai, E. A., Yeo, M., Bosch, M., Dewar, A. L., & Olson, M. F. (2001) · Nature Cell Biology · doi:10.1038/35070009 · Cited by 1,313 · see citing works
Inhibition of Human Caspases by Peptide-based and Macromolecular Inhibitors
Garcia-Calvo, M. M., Peterson, E. P., Leiting, B., Ruel, R., Nicholson, D. W., & Thornberry, N. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32608 · Cited by 980 · see citing works
Shugoshin collaborates with protein phosphatase 2A to protect cohesin
Kitajima, T. S., Sakuno, T., Ishiguro, K., Iemura, S., Natsume, T., Kawashima, S. A., & Watanabe, Y. (2006) · Nature · doi:10.1038/nature04663 · Cited by 597 · see citing works
Pallas, D. C., Shahrik, L. K., Martin, B. L., Jaspers, S. R., Miller, T. B., Brautigan, D. L., & Roberts, T. M. (1990) · Cell · doi:10.1016/0092-8674(90)90726-u · Cited by 573 · see citing works
Self-citationSontag, E., Fedorov, S. A., Kamibayashi, C., Robbins, D. J., Cobb, M. H., & Mumby, M. C. (1993) · Cell · doi:10.1016/0092-8674(93)90533-v · Cited by 510 · see citing works
Identification of specific PP2A complexes involved in human cell transformation
Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00026-1 · Cited by 325 · see citing works
Self-citationActions of PP2A on the MAP kinase pathway and apoptosis are mediated by distinct regulatory subunits
Silverstein, A. M., Barrow, C. A., Davis, A. J., & Mumby, M. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.072071699 · Cited by 276 · see citing works
Regulators of Serine / Threonine Protein Phosphatases at the Dawn of a Clinical Era?
Honkanen, R. E., & Golden, T. A. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023368836 · Cited by 261 · see citing works
Control of Protein Phosphatase 2A by Simian Virus 40 Small-t Antigen
Yang, S., Lickteig, R. L., Estes, R., Rundell, K., Walter, G., & Mumby, M. C. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.4.1988-1995.1991 · Cited by 246 · see citing works
Tolstykh, T., Lee, J., Vafai, S. B., & Stock, J. B. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5682 · Cited by 233 · see citing works
Self-citationOgris, E., Du, X., Nelson, K. C., Mak, E. K., Yu, X. X., Lane, W. S., & Pallas, D. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14382 · Cited by 191 · see citing works
Self-citationLee, J., & Stock, J. B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36497-x · Cited by 189 · see citing works
Self-citationWu, J., Tolstykh, T., Lee, J., Boyd, K., Stock, J. B., & Broach, J. R. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5672 · Cited by 186 · see citing works
Self-citationProtein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast
Minshull, J., Straight, A. F., Rudner, A. D., Dernburg, A. F., Belmont, A. S., & Murray, A. W. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70784-7 · Cited by 181 · see citing works
BRYANT, J. C., Westphal, R. S., & Wadzinski, B. E. (1999) · Biochemical Journal · doi:10.1042/bj3390241 · Cited by 173 · see citing works
The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo.
Favre, B., Zołnierowicz, S., Turowski, P., & Hemmings, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34009-7 · Cited by 166 · see citing works
Critical Role for Protein Phosphatase 2A Heterotrimers in Mammalian Cell Survival*
Strack, S., Cribbs, J., & Gomez, L. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408015200 · Cited by 160 · see citing works
Yu, X. X., Du, X., Moreno, C. S., Green, R. E., Ogris, E., Feng, Q., Chou, L., McQuoid, M. J., & Pallas, D. C. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.1.185 · Cited by 160 · see citing works
Self-citationTurowski, P., Fernandez, A., Favre, B., Lamb, N. J. C., & Hemmings, B. A. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.2.397 · Cited by 147 · see citing works
BAERE, I. D., Derua, R., Janssens, V., Hoof, C. A. V., Waelkens, E., Merlevede, W. J., & Goris, J. (1999) · Biochemistry · doi:10.1021/bi991646a · Cited by 145 · see citing works
Shtrichman, R., Sharf, R., Barr, H. M., Dobner, T., & Kleinberger, T. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10080 · Cited by 142 · see citing works
Lee, J., Chen, Y., Tolstykh, T., & Stock, J. B. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.6043 · Cited by 138 · see citing works
Self-citationLi, X., Scuderi, A., Letsou, A., & Virshup, D. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.11.3674-3684.2002 · Cited by 135 · see citing works
Ogris, E., Gibson, D. M., & Pallas, D. C. (1997) · Oncogene · doi:10.1038/sj.onc.1201259 · Cited by 134 · see citing works
Self-citationAdenovirus Type 5 E4 Open Reading Frame 4 Protein Induces Apoptosis in Transformed Cells
Shtrichman, R., & Kleinberger, T. (1998) · Journal of Virology · doi:10.1128/jvi.72.4.2975-2982.1998 · Cited by 133 · see citing works
Wang, Y., & Burke, D. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.2.620 · Cited by 132 · see citing works
Wei, H., Ashby, D. G., Moreno, C. S., Ogris, E., Yeong, F. M., Corbett, A. H., & Pallas, D. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008694200 · Cited by 128 · see citing works
Self-citationXie, H., & Clarke, S. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42124-7 · Cited by 123 · see citing works
Yan, Y., Shay, J. W., Wright, W. E., & Mumby, M. C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.24.15220 · Cited by 116 · see citing works
Inhibition of cdc2 activation by INH/PP2A.
Lee, T. H., Turck, C. W., & Kirschner, M. W. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.3.323 · Cited by 107 · see citing works
Marcellus, R. C., Chan, H. H. L., Paquette, D., Thirlwell, S. W.-L., Boivin, D., & Branton, P. E. (2000) · Journal of Virology · doi:10.1128/jvi.74.17.7869-7877.2000 · Cited by 102 · see citing works
Protein Phosphatase 2A Regulates Apoptosis in Intestinal Epithelial Cells
Ray, R. M., Bhattacharya, S., & Johnson, L. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503041200 · Cited by 76 · see citing works
Campbell, K. S., Auger, K. R., Hemmings, B. A., Roberts, T. M., & Pallas, D. C. (1995) · Journal of Virology · doi:10.1128/jvi.69.6.3721-3728.1995 · Cited by 73 · see citing works
Self-citationNunbhakdi‐Craig, V., Schüchner, S., Sontag, J., Montgomery, L. G., Pallas, D. C., Juno, C., Mudrak, I., Ogris, E., & Sontag, E. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04503.x · Cited by 72 · see citing works
Self-citationPhosphatase 2A Negatively Regulates Mitotic Exit inSaccharomyces cerevisiae
Wang, Y., & Ng, T.-Y. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-12-1109 · Cited by 72 · see citing works
Shtrichman, R., Sharf, R., & Kleinberger, T. (2000) · Oncogene · doi:10.1038/sj.onc.1203705 · Cited by 68 · see citing works
Chatfield, K. C., & Eastman, A. R. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.003 · Cited by 65 · see citing works
Xie, H., & Clarke, S. G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38660-0 · Cited by 64 · see citing works
Yellman, C. M., & Burke, D. J. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-04-0336 · Cited by 62 · see citing works
Cayla, X., Ballmer‐Hofer, K., Merlevede, W. J., & Goris, J. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17922.x · Cited by 51 · see citing works
Gil-Bernabé, A. M., Romero, F., Limón‐Mortés, M. C., & Tortolero, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01904-05 · Cited by 47 · see citing works
Evans, D. R., & Hemmings, B. A. (2000) · Molecular Genetics and Genomics · doi:10.1007/s004380000302 · Cited by 47 · see citing works
Bonness, K., Aragon, I. V., Rutland, B. M., Ofori-Acquah, S. F., Dean, N. M., & Honkanen, R. E. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0273 · Cited by 45 · see citing works
Gentry, M. S., Li, Y., Wei, H., Syed, F. F., Patel, S. H., Hallberg, R. L., & Pallas, D. C. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.6.1029-1040.2005 · Cited by 45 · see citing works
Self-citationFloer, M., & Stock, J. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1052 · Cited by 43 · see citing works
Zhu, T., Matsuzawa, S., Mizuno, Y., Kamibayashi, C., Mumby, M. C., Andjelković, N., Hemmings, B. A., Onoé, K., & Kikuchi, K. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.9835 · Cited by 41 · see citing works
Xie, H., & Clarke, S. G. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2383 · Cited by 36 · see citing works
Glenn, G. M., & Eckhart, W. (1995) · Journal of Virology · doi:10.1128/jvi.69.6.3729-3736.1995 · Cited by 35 · see citing works
Li, M., & Damuni, Z. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2031 · Cited by 34 · see citing works
Kalhor, H. R., Luk, K., Ramos, A., Zobel-Thropp, P. A., & Clarke, S. G. (2001) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2558 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Lee, J., Chen, Y., Tolstykh, T., and Stock, J. (1996) Proc. Natl. Acad. Sci.
- Silverstein, A. M., Barrow, C. A., Davis, A. J., and Mumby, M. C. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 4221-4226
- Shtrichman, R., Sharf, R., Barr, H., Dobner, T., and Kleinberger, T. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 10080 -10085
Cited by
Sorted by citations
Role of proline in cell wall synthesis and plant development and its implications in plant ontogeny
Kishor, P. B. K. (2015) · Frontiers in Plant Science · doi:10.3389/fpls.2015.00544 · Cited by 386 · see citing works
PP2A as a master regulator of the cell cycle
Wlodarchak, N., & Xing, Y. (2016) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2016.1143913 · Cited by 366 · see citing works
All roads lead to <scp>PP</scp>2A: exploiting the therapeutic potential of this phosphatase
Sangodkar, J., Farrington, C. C., McClinch, K., Galsky, M. D., Kastrinsky, D. B., & Narla, G. (2016) · The FEBS Journal · doi:10.1111/febs.13573 · Cited by 312 · see citing works
Protein phosphatase 2A dysfunction in Alzheimer’s disease
Sontag, J.-M., & Sontag, E. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00016 · Cited by 304 · see citing works
Structural mechanism of demethylation and inactivation of protein phosphatase 2A
Xing, Y., Li, Z., Chen, Y., Stock, J. B., Jeffrey, P. D., & Shi, Y. (2008) · Cell · doi:10.1016/j.cell.2008.02.041 · Cited by 206 · see citing works
Sents, W., Ivanova, E., Lambrecht, C., Haesen, D., & Janssens, V. (2013) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08579.x · Cited by 204 · see citing works
The structural basis for tight control of PP2A methylation and function by LCMT-1
Stanevich, V., Jiang, L., Satyshur, K. A., Li, Y., Jeffrey, P. D., Li, Z., Menden, P., Semmelhack, M. F., & Xing, Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.12.030 · Cited by 142 · see citing works
Protein phosphatase 2A regulatory subunits and cancer
Eichhorn, P. J. A., Creyghton, M. P., & Bernards, R. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2008.05.005 · Cited by 513 · see citing works
The metabolic advantage of tumor cells
Israël, M., & Schwartz, L. H. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-70 · Cited by 125 · see citing works
Physiologic functions of PP2A: Lessons from genetically modified mice
Reynhout, S., & Janssens, V. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.07.010 · Cited by 124 · see citing works
Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone
Guo, F., Stanevich, V., Wlodarchak, N., Sengupta, R., Jiang, L., Satyshur, K. A., & Xing, Y. (2014) · Cell Research · doi:10.1038/cr.2013.138 · Cited by 100 · see citing works
PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer
(2019) · Advances in Cancer Research · doi:10.1016/bs.acr.2019.03.009 · Cited by 93 · see citing works
Lillo, C., Kataya, A. R. A., HEIDARI, B., Creighton, M. T., Nemie-Feyissa, D., Ginbot, Z., & Jonassen, E. M. (2014) · Plant Cell & Environment · doi:10.1111/pce.12364 · Cited by 84 · see citing works
Sontag, J., Nunbhakdi‐Craig, V., Montgomery, L. G., Arning, E., Bottiglieri, T., & Sontag, E. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2816-08.2008 · Cited by 77 · see citing works
The basic biology of PP2A in hematologic cells and malignancies
Haesen, D., Sents, W., Lemaire, K., Hoorne, Y., & Janssens, V. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00347 · Cited by 73 · see citing works
Shin, J. H., Park, C. W., Yoon, G., Hong, S. M., & Choi, K. Y. (2018) · Oncogenesis · doi:10.1038/s41389-018-0064-4 · Cited by 70 · see citing works
Wandzioch, E., Pusey, M., Werda, A., Bail, S., Bhaskar, A., Nestor, M., Yang, J., & Rice, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3130 · Cited by 62 · see citing works
Jackson, J. B., & Pallas, D. C. (2012) · Neoplasia · doi:10.1593/neo.12768 · Cited by 60 · see citing works
Self-citationSontag, J., Nunbhakdi‐Craig, V., Mitterhuber, M., Ogris, E., & Sontag, E. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07049.x · Cited by 57 · see citing works
Hwang, J., Lee, J. A., & Pallas, D. C. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.739920 · Cited by 56 · see citing works
Self-citationAssembly and structure of protein phosphatase 2A
Shi, Y. (2009) · Science in China Series C Life Sciences · doi:10.1007/s11427-009-0018-3 · Cited by 55 · see citing works
Xu, F. Y., Kong, D., He, X., Zhang, Z., Han, M., Xie, X., Wang, P., Cheng, H., Tao, M., Zhang, L., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja3069243 · Cited by 52 · see citing works
Targeting the epigenetic machinery of cancer cells
Montenegro, M. F., Sánchez‐del‐Campo, L., Fernández-Pérez, M. P., Sáez‐Ayala, M., Cabezas‐Herrera, J., & Rodríguez‐López, J. N. (2014) · Oncogene · doi:10.1038/onc.2013.605 · Cited by 51 · see citing works
Methylation-regulated decommissioning of multimeric PP2A complexes
Wu, C.-G., Zheng, A., Jiang, L., Rowse, M., Stanevich, V., Chen, H., Li, Y., Satyshur, K. A., Johnson, B., Gu, T.-J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02405-3 · Cited by 45 · see citing works
Sontag, J., Wasek, B. L., Taleski, G., Smith, J. L., Arning, E., Sontag, E., & Bottiglieri, T. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00214 · Cited by 47 · see citing works
Shan, J., Zhu, M., Shi, M. Y., Gao, J., & Lin, H. (2009) · Theoretical and Applied Genetics · doi:10.1007/s00122-009-1092-4 · Cited by 45 · see citing works
Li, S.-Y., Brignole, C., Marcellus, R., Thirlwell, S., Binda, O., McQuoid, M., Ashby, D., Chan, H. L. B., Zhang, Z., Miron, M.-J., et al. (2009) · Journal of Virology · doi:10.1128/jvi.00711-09 · Cited by 56 · see citing works
Self-citationAltering phosphorylation in cancer through PP2A modifiers
Johnson, H., Narayan, S., & Sharma, A. K. (2024) · Cancer Cell International · doi:10.1186/s12935-023-03193-1 · Cited by 41 · see citing works
Dudiki, T., Kadunganattil, S., Ferrara, J. K., Kline, D., & Vijayaraghavan, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141961 · Cited by 35 · see citing works
Javadpour, P., Dargahi, L., Ahmadiani, A., & Ghasemi, R. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03063-y · Cited by 35 · see citing works
Liu, C., Wang, Q., Zong, D., Pei, S., Yan, Y., Yan, M., Sun, L., Hao, Y.-Y., Mao, M., Xing, W., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.05.010 · Cited by 32 · see citing works
Emerging insights into serine/threonine-specific phosphoprotein phosphatase function and selectivity
Kokot, T., & Köhn, M. (2022) · Journal of Cell Science · doi:10.1242/jcs.259618 · Cited by 30 · see citing works
Regulation and role of the PP2A-B56 holoenzyme family in cancer
Peris, I., Romero-Murillo, S., Vicente, C., Narla, G., & Odero, M. D. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188953 · Cited by 29 · see citing works
Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation
Lyons, S. P., Greiner, E. C., Cressey, L. E., Adamo, M. E., & Kettenbach, A. N. (2021) · Scientific Reports · doi:10.1038/s41598-021-02456-z · Cited by 27 · see citing works
Cellular inhibitors of Protein Phosphatase PP2A in cancer.
Haesen, D., Sents, W., Ivanova, E., Lambrecht, C., & Janssens, V. (2012) · Lirias · Cited by 24 · see citing works
Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily
Nasa, I., & Kettenbach, A. N. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200177 · Cited by 21 · see citing works
Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities
Sergienko, N. M., Donner, D. G., Delbridge, L. M. D., McMullen, J. R., & Weeks, K. L. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110213 · Cited by 19 · see citing works
Characterization of seed proteome in Brachypodium distachyon
Wang, K., Han, X., Dong, K., Gao, L., Li, H., Ma, W., Yan, Y., & Ye, X. (2010) · Journal of Cereal Science · doi:10.1016/j.jcs.2010.05.001 · Cited by 18 · see citing works
Lee, J. A., Wang, Z., Sambo, D., Bunting, K. D., & Pallas, D. C. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002012 · Cited by 16 · see citing works
Self-citationTeng, J., Chen, L., Yang, F., Gao, P., Yu, P., Jiang, Q., Xu, Y., Xia, W., & Yu, D. (2024) · Food Research International · doi:10.1016/j.foodres.2024.114505 · Cited by 16 · see citing works
Protein carboxyl methylation and the biochemistry of memory
Li, Z., & Stock, J. B. (2009) · Biological Chemistry · doi:10.1515/bc.2009.133 · Cited by 16 · see citing works
MacKay, K. B., Tu, Y., Young, S. G., & Clarke, S. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065967 · Cited by 14 · see citing works
Kranias, G., Watt, L. F., Carpenter, H., Holst, J., Ludowyke, R. I., Strack, S., Sim, A. T. R., & Verrills, N. M. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.07.017 · Cited by 13 · see citing works
A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size
Xia, X., Gholkar, A. A., Senese, S., & Torres, J. Z. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1026487 · Cited by 13 · see citing works
Li, Y., Balakrishnan, V. K., Rowse, M., Wu, C.-G., Bravos, A. P., Yadav, V. K., Ivarsson, Y., Strack, S., Novikova, I. V., & Xing, Y. (2022) · eLife · doi:10.7554/elife.79736 · Cited by 11 · see citing works
Rosales, M., Rodríguez‐Ulloa, A., Pérez, G. V., Besada, V., Soto, T., Ramos, Y., González, L. J., Zettl, K., Wiśniewski, J. R., Yang, K., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.834814 · Cited by 9 · see citing works
Martin, M., Kettmann, R., & Dequiedt, S. (2010) · ORBi (University of Liège) · Cited by 10 · see citing works
H2O2 induces PP2A demethylation to downregulate mTORC1 signaling in HEK293 cells
Tang, S., Fu, Q., Wang, X., Liang, Z., Cai, H., Mo, L., Huang, Y., Liang, B., Wei, X., Ao, Q., et al. (2018) · Cell Biology International · doi:10.1002/cbin.10987 · Cited by 9 · see citing works
On the metabolic origin of cancer: substances that target tumor metabolism
Israël, M., & Schwartz, L. H. (2011) · Biomedical Research-tokyo · Cited by 8 · see citing works
Protein phosphatases and their targets: Comprehending the interactions in plant signaling pathways
Saini, L. K., Bheri, M., & Pandey, G. K. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2022.11.003 · Cited by 6 · see citing works
A Novel Role of PP2A Methylation in the Regulation of Tight Junction Assembly and Integrity
Schuhmacher, D., Sontag, J., & Sontag, E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.911279 · Cited by 5 · see citing works
Creighton, M. T., Nemie-Feyissa, D., Zaman, N., Johansen, S. S., Dysjaland, H., Heidari, B., & Lillo, C. (2022) · Journal of Plant Physiology · doi:10.1016/j.jplph.2022.153843 · Cited by 6 · see citing works
LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma
Zhang, N., Lu, C., Mo, J., Wang, X., Liao, S., Liang, N., Feng, M., Tang, T., Wu, Y., Li, Y., et al. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101572 · Cited by 5 · see citing works
Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1
Tang, S., Lu, C., Mo, L., Wang, X., Liang, Z., Fu, Q., Liu, Y., Liu, Y., Huang, H., Huang, Y., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.10.029 · Cited by 3 · see citing works
(2014) · Cancer Cell & Microenvironment · doi:10.14800/ccm.299 · Cited by 2 · see citing works
Voronkov, M. V., Suslov, O., Parcha, P. K., Shastri, V. M., & Lamba, J. K. (2026) · ASPET Discovery · doi:10.1016/j.aspetd.2026.100026 · Cited by 1 · see citing works
A small molecule inhibitor of leucine carboxyl methyltransferase-1 inhibits cancer cell survival
Arosarena, O. A., Sarıbaş, A. S., & Papadopoulos, E. P. (2024) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2024.1278163 · Cited by 1 · see citing works
SERINE/THREONINE PHOSPHATASES: ROLE IN SPERMATOGENESIS AND SPERM FUNCTION
Dudiki, T. (2014) · OhioLink ETD Center (Ohio Library and Information Network)
Xing, Y., Li, Y., Rowse, M., Wu, C.-G., Bravos, A. P., Ivarsson, Y., & Strack, S. (2021) · Research Square · doi:10.21203/rs.3.rs-372534/v1
PP2A Methylation is Necessary for Broad Stress TolerancePreprint
Creighton, M. T., Nemie-Feyissa, D., Zaman, N., Johansen, S. S., Dysjaland, H., Heidari, B., & Lillo, C. (2021) · Research Square · doi:10.21203/rs.3.rs-709547/v1
Leucine Carboxyl Methyltransferase
Melideo, S. L., Ha, J. Y., & Stock, J. B. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_101594
Lee, J., & Pallas, D. C. (2008) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a003862.01
Self-citationLeucine Carboxyl Methyltransferase
Melideo, S. L., Ha, J. Y., & Stock, J. B. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6438-9_101594-1
Lyu, Y., Talwar, V., Yang, Y., Kang, S.-S., Li, S., Salman, S., Drehmer, D., Wang, Y., (19800947), C. C., Ramu, V., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci205415
- Authors
- Lee, J. A., & Pallas, D. C.
- Affiliations
- Emory University (US)
- Corresponding author
- Pallas, David C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 282
- Issue
- 42
- Pages
- 30974-30984
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3516869
- OpenAlex
- W2030633377
- Cited by
- 69
- References
- 54
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 4 · 2012: 4
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Emory University
- Broad Institute
- National Institutes of Health
- National Cancer Institute (HCT116, CA57327, CA1236402, R01CA057327)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein phosphatase 2A, spindle assembly checkpoint, apoptosis, caspase activation, embryonic lethality, cell cycle regulation
- MeSH terms
- Animals, Cell Membrane, Cell Nucleus, Cell Survival, HeLa Cells, Humans, Methylation, Methyltransferases, Mitosis, Spindle Apparatus, Protease Inhibitors, Protein O-Methyltransferase, Protein Processing, Post-Translational, Thymidine, Nocodazole, Cell Death, Apoptosis, Mice, Knockout, Caspases, Embryo Loss, Protein Subunits, Tubulin Modulators, Mice, DNA Fragmentation, Protein Phosphatase 2, Caspase Inhibitors
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
