β-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases
Open accessAbstract
β-TrCP, the F-box protein of the SCF β-TrCP ubiquitin ligase (SCF, Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif (DpSGΦXpS) in various SCF β-TrCP target proteins. The Cdc25A phosphatase, a key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin-dependent degradation in response to genotoxic stress. β-TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk1 and other unknown kinases. However, Xenopus Cdc25A does not have a DSG motif at the corresponding site of human Cdc25A. Here, we report that both Xenopus Cdc25A and human Cdc25A have a previously undescribed nonphosphorylated DDG motif (DDGΦXD) for recognition by β-TrCP. When analyzed by using Xenopus eggs, the binding of β-TrCP to the DDG motif is essential for the Chk1-induced ubiquitination and degradation of Xenopus Cdc25A and also plays a role in the degradation of human Cdc25A. The DDG motif also exists in human Cdc25B phosphatase (another key cell-cycle regulator), binds β-TrCP strongly, and is essential for the ubiquitination and degradation of the (labile) phosphatase in normal conditions. We provide strong evidence that, in both Cdc25A and Cdc25B, the binding (efficiency) of β-TrCP to the DDG motif is regulated by nearby residues, while ubiquitination is regulated by other events in addition to the β-TrCP binding. Finally, our additional data suggest that β-TrCP may recognize nonphosphorylated DDG-like motifs in many other proteins, including X11L (a putative suppressor of β-amyloid production) and hnRNP-U (a pseudosubstrate of SCF β-TrCP ).
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A G2-phase DNA damage response causes claspin-dependent Chk1/2 activation and SCFβTrcP-mediated degradation of Cdc25A, arresting multiple cell-cycle transitions including the G2 checkpoint.
“The occurrence of DNA damage response in G2-phase, leads to checkpoint mediator (claspin) dependent activation of Chk1/2, followed by SCFβTrcP mediated degradation of CDK-activating phosphatase Cdc25A [341, 342], that results in arrest of multiple cell-cycle transition including the G2 checkpoint [343, 344].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [342]
The introductory passage (page unavailable) says that DNA damage activates Chk1 and Chk2, promoting SCF-dependent Cdc25A degradation, and describes β-TrCP-dependent ubiquitination. It does not establish that this response occurs specifically in G2 or that Chk1/2 activation depends on claspin. The cell-cycle-arrest clause has separate citations [343, 344] and is not assessed against this source. (LLM, conf=0.85)
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Cites
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Liu, C., Li, Y., Semënov, M. V., Han, C., Baeg, G., Tan, Y., Zhang, Z., Lin, X., & He, X. (2002) · Cell · doi:10.1016/s0092-8674(02)00685-2 · Cited by 2,066 · see citing works
PEST sequences and regulation by proteolysis
RECHSTEINER, M. C., & Rogers, S. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10031-1 · Cited by 1,645 · see citing works
Zhou, B. P., Deng, J., Xia, W., Xu, J., Li, Y. M., Gunduz, M., & Hung, M.-C. (2004) · Nature Cell Biology · doi:10.1038/ncb1173 · Cited by 1,581 · see citing works
SCF and Cullin/RING H2-Based Ubiquitin Ligases
Deshaies, R. J. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.435 · Cited by 1,238 · see citing works
The SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114 · see citing works
The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
Falck, J., Mailand, N., Syljuåsen, R. G., Bartek, J., & Lukas, J. (2001) · Nature · doi:10.1038/35071124 · Cited by 1,085 · see citing works
Winston, J. T., Strack, P. R., Beer‐Romero, P., Chu, C. Y., Elledge, S. J., & Harper, J. W. (1999) · Genes & Development · doi:10.1101/gad.13.3.270 · Cited by 949 · see citing works
Rapid Destruction of Human Cdc25A in Response to DNA Damage
Mailand, N., Falck, J., Lukas, C., Syljuåsen, R. G., Welcker, M., Bartek, J., & Lukas, J. (2000) · Science · doi:10.1126/science.288.5470.1425 · Cited by 787 · see citing works
Identification of the receptor component of the IκBα–ubiquitin ligase
Yaron, A., Hatzubai, A., Davis, M., Lavon, I., Amit, S., Manning, A. M., Andersen, J., Mann, M., Mercurio, F., & Ben‐Neriah, Y. (1998) · Nature · doi:10.1038/25159 · Cited by 654 · see citing works
Structure of a β-TrCP1-Skp1-β-Catenin Complex
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00234-x · Cited by 612 · see citing works
Insights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex
Schulman, B. A., Carrano, A. C., Jeffrey, P. D., Bowen, Z., Kinnucan, E., Finnin, M. S., Elledge, S. J., Harper, J. W., Pagano, M., & Pavletich, N. P. (2000) · Nature · doi:10.1038/35042620 · Cited by 610 · see citing works
Sørensen, C. S., Syljuåsen, R. G., Falck, J., Schroeder, T., Rönnstrand, L., Khanna, K. K., Zhou, B.-B., Bártek, J., & Lukas, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00048-5 · Cited by 560 · see citing works
An F‐box protein, FWD1, mediates ubiquitin‐dependent proteolysis of β‐catenin
Kitagawa, M., Hatakeyama, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., Nakamichi, I., Kikuchi, A., Nakayama, K.-I., & Nakayama, K. (1999) · The EMBO Journal · doi:10.1093/emboj/18.9.2401 · Cited by 529 · see citing works
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCF <sup>β-TrCP</sup>
Watanabe, N., Arai, H., Nishihara, Y., Taniguchi, M., Watanabe, N., Hunter, T., & Osada, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307700101 · Cited by 472 · see citing works
Zhao, H., Watkins, J. L., & Piwnica-Worms, H. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182557299 · Cited by 459 · see citing works
Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage
Busino, L., Donzelli, M., Chiesa, M., Guardavaccaro, D., Ganoth, D., Valerio Dorrello, N., Hershko, A., Pagano, M., & Draetta, G. F. (2003) · Nature · doi:10.1038/nature02082 · Cited by 447 · see citing works
Regulating mammalian checkpoints through Cdc25 inactivation
Donzelli, M., & Draetta, G. F. (2003) · EMBO Reports · doi:10.1038/sj.embor.embor887 · Cited by 435 · see citing works
Maniatis, T. (1999) · Genes & Development · doi:10.1101/gad.13.5.505 · Cited by 423 · see citing works
SCF<sup>β-TRCP</sup> links Chk1 signaling to degradation of the Cdc25A protein phosphatase
Jin, J., Shirogane, T., Xu, L., Nalepa, G., Qin, J., Elledge, S. J., & Harper, J. W. (2003) · Genes & Development · doi:10.1101/gad.1157503 · Cited by 340 · see citing works
Margottin-Goguet, F., Hsu, J. Y., Loktev, A. V., Hsieh, H.-M., Reimann, J. D. R., & Jackson, P. K. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00153-9 · Cited by 337 · see citing works
Regulation of G2/M events by Cdc25A through phosphorylation‐dependent modulation of its stability
Mailand, N., Podtelejnikov, A. V., Groth, A., Mann, M., Bartek, J., & Lukas, J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf567 · Cited by 315 · see citing works
The many faces of β-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer
Fuchs, S. Y., Spiegelman, V. S., & Kumar, S. (2004) · Oncogene · doi:10.1038/sj.onc.1207389 · Cited by 311 · see citing works
The cdc25B phosphatase is essential for the G 2/M phase transition in human cells
Lammer, C., Wagerer, S., Saffrich, R., Mertens, D., Ansorge, W. J., & Hoffmann, I. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.16.2445 · Cited by 305 · see citing works
Moshe, Y., Boulaire, J., Pagano, M., & Hershko, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402442101 · Cited by 213 · see citing works
Cdc25A phosphatase: combinatorial phosphorylation, ubiquitylation and proteolysis
Busino, L., Chiesa, M., Draetta, G. F., & Donzelli, M. (2004) · Oncogene · doi:10.1038/sj.onc.1207394 · Cited by 210 · see citing works
Molinari, M., Mercurio, C., Dominguez, J., Goubin, F., & Draetta, G. F. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd018 · Cited by 203 · see citing works
Dual mode of degradation of Cdc25 A phosphatase
Donzelli, M., Squatrito, M., Ganoth, D., Hershko, A., Pagano, M., & Draetta, G. F. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf491 · Cited by 194 · see citing works
Orian, A., Gonen, H., Bercovich, B., Fajerman, I., Eytan, E., Israël, A., Mercurio, F., Iwaï, K., Schwartz, A. L., & Ciechanover, A. J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2580 · Cited by 174 · see citing works
Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism.
Uto, K., Inoue, D., Shimuta, K., Nakajo, N., & Sagata, N. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600328 · Cited by 134 · see citing works
Self-citationShimuta, K., Nakajo, N., Uto, K., Hayano, Y., Okazaki, K., & Sagata, N. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf357 · Cited by 126 · see citing works
Self-citationSuzuki, H., Chiba, T., Kobayashi, M., Takeuchi, M., Suzuki, T., Ichiyama, A., Ikenoue, T., Omata, M., Furuichi, K., & Tanaka, K. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0289 · Cited by 122 · see citing works
Pseudosubstrate regulation of the SCF β-TrCP ubiquitin ligase by hnRNP-UPreprint
Davis, M., Hatzubai, A., Andersen, J., Ben-Shushan, E., Fisher, G. Z., Yaron, A., Bauskin, A. R., Mercurio, F., Mann, M., & Ben‐Neriah, Y. (2002) · Genes & Development · doi:10.1101/gad.218702 · Cited by 119 · see citing works
Gabrielli, B. G., Clark, J. M., McCormack, A. K., & Ellem, K. A. O. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28607 · Cited by 112 · see citing works
Baldin, V., Cans, C., Knibiehler, M., & Ducommun, B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.52.32731 · Cited by 103 · see citing works
Nishijima, H., Nishitani, H., Seki, T., & Nishimoto, T. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.5.1105 · Cited by 88 · see citing works
Besnard‐Guérin, C., Belaïdouni, N., Lassot, I., Ségéral, E., Jobart‐Malfait, A., Marchal, C., & Bénarous, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308068200 · Cited by 84 · see citing works
A Maternal Form of the Phosphatase Cdc25A Regulates Early Embryonic Cell Cycles in Xenopus laevis
Kim, S. H., Li, C., & Maller, J. L. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9361 · Cited by 72 · see citing works
Cytoplasmic Occurrence of the Chk1/Cdc25 Pathway and Regulation of Chk1 in Xenopus Oocytes
Oe, T., Nakajo, N., Katsuragi, Y., Okazaki, K., & Sagata, N. (2001) · Developmental Biology · doi:10.1006/dbio.2000.9968 · Cited by 50 · see citing works
Self-citationTaru, H., & Suzuki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312007200 · Cited by 44 · see citing works
Mantovani, F., & Banks, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302799200 · Cited by 44 · see citing works
Sagata, N. (2002) · Science · doi:10.1126/science.1079225 · Cited by 19 · see citing works
Self-citationOkazaki, K., Hayashida, K., Iwashita, J., Harano, M., Furuno, N., & Sagata, N. (1996) · Gene · doi:10.1016/0378-1119(96)00344-7 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Moshe, Y., Boulaire, J., Pagano, M. & Hershko, A. (2004) Proc. Natl. Acad. Sci. USA 101, 7937-7942.
- Zhao, H., Watkins, J. L. & Piwnica-Worms, H. (2002) Proc. Natl. Acad. Sci. USA 99, 14795-14800.
- Watanabe, N., Arai, H., Nishihara, Y., Taniguchi, M., Watanabe, N., Hunter, T. & Osada, H. (2004) Proc. Natl. Acad. Sci. USA 101, 4419-4424.
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Nakayama, K. I., & Nakayama, K. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1881 · Cited by 1,441 · see citing works
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Rastogi, R. P., Richa, Kumar, A., Tyagi, M. B., & Sinha, R. P. (2010) · Journal of Nucleic Acids · doi:10.4061/2010/592980 · Cited by 1,329 · see citing works
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Frescas, D., & Pagano, M. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2396 · Cited by 886 · see citing works
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Boutros, R., Lobjois, V., & Ducommun, B. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2169 · Cited by 710 · see citing works
Roey, K. V., Uyar, B., Weatheritt, R. J., Dinkel, H., Seiler, M., Budd, A., Gibson, T. J., & Davey, N. E. (2014) · Chemical Reviews · doi:10.1021/cr400585q · Cited by 496 · see citing works
McMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601119200 · Cited by 489 · see citing works
Rada, P., Rojo, A. I., Evrard‐Todeschi, N., Innamorato, N. G., Cotte, A., Jaworski, T., Tobón-Velasco, J. C., Devijver, H., García‐Mayoral, M. F., LEUVEN, F. V., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00180-12 · Cited by 474 · see citing works
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Vucic, D., Dixit, V. M., & Wertz, I. E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3143 · Cited by 451 · see citing works
Tong, K. I., Padmanabhan, B., Kobayashi, A., Shang, C., Hirotsu, Y., Yokoyama, S., & Yamamoto, M. P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00753-07 · Cited by 447 · see citing works
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Boutros, R., Dozier, C., & Ducommun, B. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.02.003 · Cited by 417 · see citing works
Shirogane, T., Jin, J., Cambronne, X. A., & Harper, J. W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502862200 · Cited by 293 · see citing works
Tempé, D., Casas, M., Karaz, S., Blanchet-Tournier, M.-F., & Concordet, J.-P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02183-05 · Cited by 249 · see citing works
Stracker, T. H., Usui, T., & Petrini, J. H. J. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.012 · Cited by 245 · see citing works
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Inuzuka, H., Tseng, A., Gao, D., Zhai, B., Zhang, Q. H., Shaik, S., Wan, L., Cambronne, X. A., Mock, C. S., Yin, H., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.06.015 · Cited by 205 · see citing works
Sarkar, S., Dey, B. K., & Dutta, A. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-01-0062 · Cited by 204 · see citing works
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Gao, M., & Karin, M. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.017 · Cited by 159 · see citing works
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Guharoy, M., Bhowmick, P., Sallam, M., & Tompa, P. (2016) · Nature Communications · doi:10.1038/ncomms10239 · Cited by 145 · see citing works
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Pal, S., Bhattacharjee, A., Ali, A., Mandal, N. C., Mandal, S. C., & Pal, M. (2014) · Journal of Inflammation · doi:10.1186/1476-9255-11-23 · Cited by 117 · see citing works
Liu, P., Barkley, L. R., Day, T. A., Bi, X., Slater, D., Alexandrow, M. G., Nasheuer, H., & Vaziri, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602982200 · Cited by 97 · see citing works
Kruiswijk, F., Yuniati, L., Magliozzi, R., Low, T. Y., Lim, R., Bolder, R., Mohammed, S., Proud, C. G., Heck, A. J. R., Pagano, M., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2002718 · Cited by 91 · see citing works
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Tan, M., Gallegos, J. R., Gu, Q., Huang, Y., Li, J., Jin, Y., Lu, H., & Sun, Y. (2006) · Neoplasia · doi:10.1593/neo.06568 · Cited by 89 · see citing works
Shi, J., Liu, Y., Xu, X., Zhang, W., Yu, T., Jia, J., & Liu, C. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00373-15 · Cited by 86 · see citing works
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Setoyama, D., Yamashita, M., & Sagata, N. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706952104 · Cited by 82 · see citing works
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Meyer, L., Deau, B., Forejtníková, H., Dumènil, D., Margottin-Goguet, F., Lacombe, C., Mayeux, P., & Verdier, F. (2007) · Blood · doi:10.1182/blood-2006-10-055350 · Cited by 74 · see citing works
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Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins
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Yumimoto, K., Yamauchi, Y., & Nakayama, K. I. (2020) · Cancers · doi:10.3390/cancers12051249 · Cited by 62 · see citing works
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Ribeiro, P. S., Holder, M. V., Frith, D., Snijders, A. P., & Tapon, N. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315508111 · Cited by 60 · see citing works
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Low, T. Y., Peng, M., Magliozzi, R., Mohammed, S., Guardavaccaro, D., & Heck, A. J. R. (2014) · Science Signaling · doi:10.1126/scisignal.2005882 · Cited by 55 · see citing works
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Shahab Uddin, M. S., Bhat, A. A., Krishnankutty, R., Mir, F. A., Kuliński, M., & Mohammad, R. M. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.09.008 · Cited by 55 · see citing works
Gutierrez, G. J., Vögtlin, A., Castro, A., Ferby, I., Salvagiotto, G., Ronai, Z. A., Lorca, T., & Nebreda, Á. R. (2006) · Nature Cell Biology · doi:10.1038/ncb1472 · Cited by 54 · see citing works
Gluschnaider, U., Hidas, G., Cojocaru, G., Yutkin, V., Ben‐Neriah, Y., & Pikarsky, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009060 · Cited by 44 · see citing works
CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability
Dozier, C., Mazzolini, L., Cénac, C., Froment, C., Burlet‐Schiltz, O., Besson, A., & Manenti, S. (2017) · Oncogene · doi:10.1038/onc.2016.506 · Cited by 43 · see citing works
Manavathi, B., Rayala, S. K., & Kumar, R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702309200 · Cited by 42 · see citing works
Isoda, M., Kanemori, Y., Nakajo, N., Uchida, S., Yamashita, K., Ueno, H., & Sagata, N. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-01-0008 · Cited by 42 · see citing works
Self-citationCollart, C., Smith, J. C., & Zegerman, P. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.06.010 · Cited by 38 · see citing works
Novel Insights into the Molecular Mechanisms Governing Mdm2 Ubiquitination and Destruction
Inuzuka, H., Fukushima, H., Shaik, S., & Wei, W. (2010) · Oncotarget · doi:10.18632/oncotarget.202 · Cited by 39 · see citing works
MAPK Pathway Activation Delays G2/M Progression by Destabilizing Cdc25B
Astuti, P., Soliman, T. N., Widberg, C., Payne, E., Harding, A. S., Hancock, J. F., & Gabrielli, B. G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027516 · Cited by 37 · see citing works
Uchida, S., Yoshioka, K., Kizu, R., Nakagama, H., Matsunaga, T., Ishizaka, Y., Poon, R. Y. C., & Yamashita, K. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0869 · Cited by 36 · see citing works
Kohama, Y., Saito, M., Yada, M., & Sakurai, H. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.11.017 · Cited by 35 · see citing works
DNA Damage Regulates Translation through β-TRCP Targeting of CReP
Loveless, T. B., Topacio, B. R., Vashisht, A. A., Galaang, S., Ulrich, K., Young, B. D., Wohlschlegel, J. A., & Toczyski, D. P. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005292 · Cited by 34 · see citing works
Liu, G., Zhang, Q., Li, X., Shi, M., Cai, J. L., Zhang, H., Li, J., Lin, G., Xie, W., Zhang, Y., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1927-0 · Cited by 33 · see citing works
Stolfi, C., Fina, D., Caruso, R., Caprioli, F., Fantini, M. C., Rizzo, A., Sarra, M., Pallone, F., & Monteleone, G. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn122 · Cited by 32 · see citing works
UV-induced degradation of securin is mediated by SKP1-CUL1-βTrCP E3 ubiquitin ligase
Limón‐Mortés, M. C., Mora‐Santos, M., Espina, Á. G., Pintor‐Toro, J. A., López-Román, A., Tortolero, M., & Romero, F. (2008) · Journal of Cell Science · doi:10.1242/jcs.020552 · Cited by 29 · see citing works
The neglected part of early embryonic development: maternal protein degradation
Toralová, T., Kinterová, V., Chmelíková, E., & Kaňka, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03482-2 · Cited by 28 · see citing works
Differential mitotic degradation of the CDC25B phosphatase variants
Kieffer, I., Lorenzo, C., Dozier, C., Schmitt, E., & Ducommun, B. (2007) · Oncogene · doi:10.1038/sj.onc.1210596 · Cited by 28 · see citing works
NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation
Neidel, S., Ren, H., Torres, A. A., & Smith, G. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1813504116 · Cited by 28 · see citing works
D’Annibale, S., Kim, J., Magliozzi, R., Low, T. Y., Mohammed, S., Heck, A. J. R., & Guardavaccaro, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.549535 · Cited by 26 · see citing works
Unscheduled expression of CDC25B in S-phase leads to replicative stress and DNA damage
Bugler, B., Schmitt, E., Aressy, B., & Ducommun, B. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-29 · Cited by 26 · see citing works
Ubiquitin in Cell-Cycle Regulation and Dysregulation in Cancer
Borg, N. A., & Dixit, V. M. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-040716-075607 · Cited by 25 · see citing works
Ras Regulates SCFβ-TrCP Protein Activity and Specificity via Its Effector Protein NORE1A
Schmidt, M., Donninger, H., & Clark, G. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.594283 · Cited by 23 · see citing works
Baudier, J., Jenkins, Z. A., & Robertson, S. P. (2018) · Journal of Cell Science · doi:10.1242/jcs.213959 · Cited by 23 · see citing works
Arquint, C., Cubizolles, F., Morand, A., Schmidt, A., & Nigg, E. A. (2018) · Open Biology · doi:10.1098/rsob.170253 · Cited by 23 · see citing works
SSRP1-mediated histone H1 eviction promotes replication origin assembly and accelerated development
Falbo, L., Raspelli, E., Romeo, F., Fiorani, S., Pezzimenti, F., Casagrande, F., Costa, I., Parazzoli, D., & Costanzo, V. (2020) · Nature Communications · doi:10.1038/s41467-020-15180-5 · Cited by 21 · see citing works
SCFβTrCP mediates stress-activated MAPK-induced Cdc25B degradation
Uchida, S., Watanabe, N., Kudo, Y., Yoshioka, K., Matsunaga, T., Ishizaka, Y., Nakagama, H., Poon, R. Y. C., & Yamashita, K. (2011) · Journal of Cell Science · doi:10.1242/jcs.083931 · Cited by 20 · see citing works
Plesca, D. C., Mazumder, S., Gama, V., Matsuyama, S., & Almasan, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804642200 · Cited by 19 · see citing works
Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities
Awan, A. B., Osman, M. J. A., & Khan, O. M. (2025) · Cells · doi:10.3390/cells14020069 · Cited by 18 · see citing works
Jullien, D., Bugler, B., Dozier, C., Cazalès, M., & Ducommun, B. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2453 · Cited by 18 · see citing works
DNA Damage Induces the Accumulation of Tiam1 by Blocking β-TrCP-dependent Degradation
Zhu, G., Fan, Z., Ding, M., Mu, L., Liang, J. B., Ding, Y., Fu, Y., Huang, B., & Wu, W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.553388 · Cited by 18 · see citing works
Kluge, S. F., Sauter, D., Vogl, M., Peeters, M., Li, Y., Bibollet‐Ruche, F., Hahn, B. H., & Kirchhoff, F. (2013) · Retrovirology · doi:10.1186/1742-4690-10-32 · Cited by 18 · see citing works
Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor
Paul, D., Kales, S. C., Cornwell, J. A., Afifi, M. M., Rai, G., Zakharov, A. V., Simeonov, A. M., & Cappell, S. D. (2022) · Nature Communications · doi:10.1038/s41467-022-33762-3 · Cited by 17 · see citing works
Reviriego‐Mendoza, M. M., & Frisque, R. J. (2010) · Virology · doi:10.1016/j.virol.2010.10.038 · Cited by 17 · see citing works
Mouery, R. D., Lukasik, K., Hsu, C., Bonacci, T., Bolhuis, D. L., Wang, X., Mills, C. A., Toomer, E. D., Canterbury, O. G., Robertson, K., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114510 · Cited by 17 · see citing works
Involvement of the βTrCP in the ubiquitination and stability of the HIV-1 Vpu protein
Belaïdouni, N., Marchal, C., Bénarous, R., & Besnard‐Guérin, C. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.03.195 · Cited by 16 · see citing works
SKP1 ‐ CUL1 ‐F‐box: Key molecular targets affecting disease progression
Zeng, X., Cao, J., Xu, J., Zhou, Z., Long, C., Zhou, Y., & Tang, J. (2025) · The FASEB Journal · doi:10.1096/fj.202402816rr · Cited by 15 · see citing works
Sasajima, H., Nakagawa, K., Kashiwayanagi, M., & Yokosawa, H. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00330 · Cited by 15 · see citing works
Beta-Transducin Repeats-Containing Proteins as an Anticancer Target
Kim, D. J., Yi, Y., & Seong, Y. (2023) · Cancers · doi:10.3390/cancers15174248 · Cited by 14 · see citing works
Chou, S.-T., Yen, Y., Lee, C., & Chen, M.-S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.078386 · Cited by 14 · see citing works
Cif type III effector protein: A smart hijacker of the host cell cycle
Samba‐Louaka, A., Taieb, F. E., Nougayrède, J., & Oswald, É. (2009) · Future Microbiology · doi:10.2217/fmb.09.60 · Cited by 12 · see citing works
Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer
Rodríguez-Alonso, A., Casas-Pais, A., Roca‐Lema, D., Graña, B., Romay, G., & Figueroa, A. (2020) · Cancers · doi:10.3390/cancers12113093 · Cited by 13 · see citing works
Bouché, J., Froment, C., Dozier, C., Esmenjaud, C., Lemaire, M., Monsarrat, B., Burlet‐Schiltz, O., & Ducommun, B. (2008) · Journal of Proteome Research · doi:10.1021/pr700623p · Cited by 13 · see citing works
Ng, L. Y., Ma, H. T., & Poon, R. Y. C. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.102957 · Cited by 12 · see citing works
Musgrove, E. A., & Sutherland, R. L. (2010) · Cell Cycle · doi:10.4161/cc.9.23.13889 · Cited by 11 · see citing works
Cycle on Wheels: Is APP Key to the AppBp1 Pathway?
Chen, Y., Neve, R., Zheng, H., Griffin, W. S. T., Barger, S. W., & Mrak, R. E. (2014) · PubMed · Cited by 10 · see citing works
E3 Ubiquitin Ligases in Cancer and Their Pharmacological Targeting
Ong, J. Y., & Torres, J. Z. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82883 · Cited by 8 · see citing works
Young, L. M., & Pagano, M. (2010) · Cell Cycle · doi:10.4161/cc.9.23.13934 · Cited by 8 · see citing works
Dual inhibition of Cdc2 protein kinase activation during apoptosis in Xenopus egg extracts
Tsuchiya, Y., Murai, S., & Yamashita, S. (2015) · FEBS Journal · doi:10.1111/febs.13217 · Cited by 8 · see citing works
Extracellular matrix stiffness regulates degradation of MST2 via SCF βTrCP
Fiore, A. P. Z. P., Rodrigues, A. M., Filho, H. V. R., Manucci, A. C., Ribeiro, P. D. F., Botelho, M. C. S., Vogel, C., de Oliveira, P. S. L., Pagano, M., & Bruni‐Cardoso, A. (2022) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2022.130238 · Cited by 7 · see citing works
An autonomous mathematical model for the mammalian cell cycle
Williams, K. S., Secomb, T. W., & El-Kareh, A. W. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2023.111533 · Cited by 6 · see citing works
Pickering, S., Sumner, J., Kerridge, C., Perera, M. R., & Neil, S. J. D. (2023) · mBio · doi:10.1128/mbio.03293-22 · Cited by 6 · see citing works
The Role of FBXW Subfamily of F-box Proteins in Tumorigenesis
Lau, A. W., Liu, Y., Tron, A. E., Inuzuka, H., & Wei, W. (2014) · Springer eBooks · doi:10.1007/978-3-319-05026-3_2 · Cited by 6 · see citing works
Zeng, X., Liao, Y., Huang, D., Yang, H. J., Dai, Z., Chen, Z., Luo, X., Gong, H., Huang, S., & Zhang, L. (2025) · Scientific Reports · doi:10.1038/s41598-024-84689-2 · Cited by 5 · see citing works
- Authors
- Kanemori, Y., Uto, K., & Sagata, N.
- Affiliations
- Kyushu University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-04-21
- Volume
- 102
- Issue
- 18
- Pages
- 6279-6284
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1083676
- OpenAlex
- W2110323618
- Cited by
- 128
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 2 · 2012: 6
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- dx.doi.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- β-TrCP, SCF ubiquitin ligase, CDC25A, CDC25B, ubiquitination, protein degradation, Chk1, genotoxic stress, cell cycle regulation, HNRNPU
- MeSH terms
- Checkpoint Kinase 1, Animals, Glutathione Transferase, Humans, Ovum, Protein Binding, Protein Kinases, Ubiquitins, Xenopus, Immunoblotting, Mutagenesis, DNA, Complementary, Cell Cycle Proteins, cdc25 Phosphatases, Amino Acid Motifs, Xenopus Proteins, Ubiquitin-Protein Ligases, beta-Transducin Repeat-Containing Proteins
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