The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
The APC tumour suppressor has a nuclear export function
Abstract
The adenomatous polpyposis coli (APC) protein is mutated in most colorectal tumours. Nearly all APC mutations are truncations, and many of these terminate in the mutation cluster region located halfway through the protein. In cancer cells expressing mutant APC, beta-catenin is stabilized and translocates into the nucleus to act as a transcriptional co-activator of T-cell factor. During normal development, APC also promotes the destabilization of beta-catenin and Drosophila Armadillo. It does so by binding to the Axin complex which earmarks beta-catenin/Armadillo for degradation by the proteasome pathway. APC has a regulatory role in this process, which is poorly understood. Here we show that APC contains highly conserved nuclear export signals 3' adjacent to the mutation cluster region that enable it to exit from the nucleus. This ability is lost in APC mutant cancer cells, and we provide evidence that beta-catenin accumulates in the nucleus as a result. Thus, the ability of APC to exit from the nucleus appears to be critical for its tumour suppressor function.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“As mentioned above, asymmetric membrane accumulation of Dsh is important for the non-canonical pathway and convergent extension movements.118–120”
From Wnt signal transduction pathways (2008) · cites this paper as [119]
Citations
Cites
Lessons from hereditary colorectal cancer
Kinzler, K. W., & Vogelstein, B. (1996) · Cell · doi:10.1016/s0092-8674(00)81333-1 · Cited by 4,919
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Morin, P. J., Sparks, A. B., Kořínek, V., Barker, N., Clevers, H. C., Vogelstein, B., & Kinzler, K. W. (1997) · Science · doi:10.1126/science.275.5307.1787 · Cited by 4,000
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., & Clevers, H. (1997) · Science · doi:10.1126/science.275.5307.1784 · Cited by 2,905
CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals
Fornerod, M. W. J., Ohno, M., Yoshida, M., & Mattaj, I. W. (1997) · Cell · doi:10.1016/s0092-8674(00)80371-2 · Cited by 2,086
Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β
Behrens, J., Jerchow, B., Würtele, M., Grimm, J., Asbrand, C., Wirtz, R. M., Kühl, M., Wedlich, D., & Birchmeier, W. (1998) · Science · doi:10.1126/science.280.5363.596 · Cited by 1,255
Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the Nucleus
Peifer, M., & Polakis, P. (2000) · Science · doi:10.1126/science.287.5458.1606 · Cited by 1,253
CRM1 is responsible for intracellular transport mediated by the nuclear export signal
Fukuda, M., Asano, S., Nakamura, T., Adachi, M., Yoshida, M., Yanagida, M., & Nishida, E. (1997) · Nature · doi:10.1038/36894 · Cited by 1,213
Association of the APC Tumor Suppressor Protein with Catenins
Su, L.-K., Vogelstein, B., & Kinzler, K. W. (1993) · Science · doi:10.1126/science.8259519 · Cited by 1,193
Munemitsu, S. M., Albert, I., Souza, B., Rubinfeld, B., & Polakis, P. G. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.3046 · Cited by 1,021
Hart, M. J., Santos, R. D. L., Albert, I., Rubinfeld, B., & Polakis, P. G. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70226-x · Cited by 850
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 343
The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells
de la Roche, M., Worm, J., & Bienz, M. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-199 · Cited by 108
“SW480 and HCT116 cells were fixed and stained with rabbit α-FLAG (Sigma Aldrich) or mouse monoclonal α-β-catenin C19220 (BD Transduction Laboratories) antibodies 24 hours after transfection as described [38].”
Self-citationAPC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
Parker, T. W., & Neufeld, K. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-59899-z · Cited by 107
Role of β-Catenin/T-Cell Factor-Regulated Genes in Ovarian Endometrioid Adenocarcinomas
Zhai, Y., WU, R. T., Schwartz, D. R., Darrah, D. M., Reed, H., Kolligs, F. T., Nieman, M. T., Fearon, E. R., & Cho, K. R. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62550-3 · Cited by 107
CRM1- and Ran-independent nuclear export of β-catenin
Wiechens, N., & Fagotto, F. (2001) · Current Biology · doi:10.1016/s0960-9822(00)00045-2 · Cited by 107
Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis
Wu, W. K. K., Wang, X., Cheng, A. S. L., Luo, M. X. M., Ng, S. S. M., To, K. F., Chan, F. K. L., Cho, C. H., Sung, J. J. �., & Yu, J. Q. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2012.11.009 · Cited by 111
“The tumor-suppressor activity of utant APC is compromised due to its inability to be exported rom the nucleus to the cytoplasm where it induces atenin degradation [72,73].”
BackgroundColorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review
Pandurangan, A. K., Divya, T., Kumar, K., Dineshbabu, V., Velavan, B., & Sudhandiran, G. (2018) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v10.i9.244 · Cited by 108
Kelly, K. F., Spring, C. M., Otchere, A. A., & Daniel, J. M. (2004) · Journal of Cell Science · doi:10.1242/jcs.01101 · Cited by 103
Kato, T., Satoh, S., Okabe, H., Kitahara, O., Ono, K., Kihara, C., Tanaka, T., Tsunoda, T., Yamaoka, Y., Nakamura, Y., et al. (2001) · Neoplasia · doi:10.1038/sj.neo.7900132 · Cited by 103
Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia
Senda, T., Iizuka‐Kogo, A., Onouchi, T., & Shimomura, A. (2007) · Medical Molecular Morphology · doi:10.1007/s00795-006-0352-5 · Cited by 107
β-Catenin and the morphogenesis of colorectal cancer
Brabletz, T., Jung, A., & Kirchner, T. (2002) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-002-0642-9 · Cited by 101
Levina, E. M., Oren, M., & Ben‐Ze'ev, A. (2004) · Oncogene · doi:10.1038/sj.onc.1207587 · Cited by 94
“In addition, a nuclearcytoplasmic transport of b-catenin, by a process involving APC, was also implicated in b-catenin degradation (Henderson, 2000; Rosin-Arbesfeld et al., 2000).”
BackgroundDrosophilaApc1 and Apc2 regulate Wingless transduction throughout development
Ahmed, Y. F., Nouri, A., & Wieschaus, E. F. (2002) · Development · doi:10.1242/dev.129.7.1751 · Cited by 93
Wnt signaling from membrane to nucleus: β-catenin caught in a loop
Jamieson, C., Sharma, M., & Henderson, B. R. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.03.001 · Cited by 93
RanBP3 enhances nuclear export of active β-catenin independently of CRM1
Hendriksen, J., Fagotto, F., van der Velde, H., van Schie, M., Noordermeer, J. N., & Fornerod, M. W. J. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200502141 · Cited by 91
“1 C) indicated that RanBP3 may act on JCB • VOLUME 171 • NUMBER 5 • 2005788 the Wnt signaling pathway independently of CRM1, which has been reported to play a role in -catenin nuclear export via interaction with APC (Henderson, 2000; Neufeld et al., 2000; Rosin-Arbesfeld et al., 2000).”
BackgroundGroucho binds two conserved regions of LEF-1 for HDAC-dependent repression
Arce, L., Pate, K. T., & Waterman, M. L. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-159 · Cited by 91
Caspi, M., Zilberberg, A., Eldar-Finkelman, H., & Rosin‐Arbesfeld, R. (2008) · Oncogene · doi:10.1038/sj.onc.1211026 · Cited by 89
“Although several components of the b-catenin destruction complex such as Axin, APC and Dsh have been shown to enter the nucleus and regulate the subcellular localization and function of b-catenin (Henderson, 2000; Rosin-Arbesfeld et al., 2000; Cong and Varmus, 2004; Wiechens et al., 2004; Itoh et al., 2005), a correla…”
BackgroundSelf-citationAPC shuttling to the membrane, nucleus and beyond
Brocardo, M. G., & Henderson, B. R. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.09.002 · Cited by 95
Fukuyama, R., Niculaita, R., Ng, K. P., Obusez, E. C., Sanchez, J., Kalady, M. F., Aung, P. P., Casey, G., & Sizemore, N. (2008) · Oncogene · doi:10.1038/onc.2008.204 · Cited by 88
Li, G., & Iyengar, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202355799 · Cited by 89
He, X. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00165-5 · Cited by 86
Biomedical Applications of Poisonous Plant Research
James, L. F., Panter, K. E., Gaffield, W., & Molyneux, R. J. (2004) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0308206 · Cited by 87
Protein kinase B phosphorylates AHNAK and regulates its subcellular localization
Sussman, J., Stokoe, D., Ossina, N., & Shtivelman, E. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200105121 · Cited by 87
The MyoD-Inducible p204 Protein Overcomes the Inhibition of Myoblast Differentiation by Id Proteins
Liu, C.-J., Ding, B., Wang, H., & Lengyel, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.9.2893-2905.2002 · Cited by 84
“It is possible that p204, which binds the Id proteins, mediates the translocation of the bound Id proteins from the nucleus to the cytoplasm, thereby accelerating their degradation by the ubiquitin pathway (7, 19, 41, 61).”
BackgroundNucleo-cytoplasmic Shuttling of Axin, a Negative Regulator of the Wnt-β-Catenin Pathway
Wiechens, N., Heinle, K., Englmeier, L., Schohl, A., & Fagotto, F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307253200 · Cited by 84
The Third 20 Amino Acid Repeat Is the Tightest Binding Site of APC for β-Catenin
Liu, J., Xing, Y., Hinds, T. R., Zheng, J., & Xu, W. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.04.064 · Cited by 89
Wang, Y., & Gilmore, T. D. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(01)00077-5 · Cited by 83
APC Mutations as a Potential Biomarker for Sensitivity to Tankyrase Inhibitors in Colorectal Cancer
Tanaka, N., Mashima, T., Mizutani, A., Sato, A., Aoyama, A., Gong, B., Yoshida, H., Muramatsu, Y., Nakata, K., Matsuura, M., et al. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0578 · Cited by 80
“These mice produce a short APC (1-580) mutant, which lacks all 20-AARs and is classified as tankyrase inhibitor–sensitive, according to our present study.”
BackgroundGu, M., Jiang, H., Tan, M., Yu, L., Xu, N., Li, Y., Wu, H., Hou, Q., & Dai, C. (2023) · Nature Communications · doi:10.1038/s41467-023-42476-z · Cited by 83
“Conversely, APC and AXIN1 harbor functional NES sequences and facilitate the nuclear export of β -catenin 30,31 .”
A Drosophila APC tumour suppressor homologue functions in cellular adhesion
Hamada, F., & Bienz, M. (2002) · Nature Cell Biology · doi:10.1038/ncb755 · Cited by 84
“The reduction of nuclear β-catenin and β-catenin-mediated transcription depends on a nuclear export function of APC (ref”
BackgroundSelf-citationPygopus Residues Required for its Binding to Legless Are Critical for Transcription and Development
Townsley, F. M., Thompson, B. J., & Bienz, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309722200 · Cited by 78
Self-citationThe genetic pathogenesis of colorectal cancer
Lynch, J. P., & Hoops, T. C. (2002) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(02)00029-1 · Cited by 78
“APC possesses nuclear import and export functions; it is in fact required for the shuttling of b-catenin from the nucleus to the cytoplasm [83,84] where it joins the multi-protein complex.”
BackgroundApoptosis in neural crest cells by functional loss of APC tumor suppressor gene
Hasegawa, S., Sato, T., Akazawa, H., Okada, H., Maeno, A., Ito, M., Sugitani, Y., Shibata, H., Miyazaki, J., Katsuki, M., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012264999 · Cited by 78
Regulation of p120-catenin nucleocytoplasmic shuttling activity
Roczniak-Ferguson, A., & Reynolds, A. B. (2003) · Journal of Cell Science · doi:10.1242/jcs.00724 · Cited by 79
“APC also enters the nucleus by a mechanism that is dependant on its Arm domain (Galea et al., 2001; Rosin-Arbesfeld et al., 2000).”
BackgroundLZTS2 Is a Novel β-Catenin-Interacting Protein and Regulates the Nuclear Export of β-Catenin
Thyssen, G. N., Li, T.-H., Lehmann, L. W., Zhuo, M., Sharma, M., & Sun, Z. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01031-06 · Cited by 77
“However, the LZTS2(1-437) and LZTS2(164-437) mutants showed virtually no interaction with the armadillo repeats of -catenin, suggesting that the region between amino acids 447 and 669 is required for the interaction.”
BackgroundInfluentialNew perspectives on APC control of cell fate and proliferation in colorectal cancer
Phelps, R. A., Broadbent, T. J., Stafforini, D. M., & Jones, D. A. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9278 · Cited by 76
Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner
Lee, Y., Kim, N. H., Cho, E. S., Yang, J. H., Cha, Y. H., Kang, H. E., Yun, J. S., Cho, S. B., Lee, S.-H., Paclíková, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04757-w · Cited by 74
Wnt/β-catenin signaling in colorectal cancer: Is therapeutic targeting even possible?
Disoma, C., Zhou, Y., Li, S., Peng, J., & Xia, Z. (2022) · Biochimie · doi:10.1016/j.biochi.2022.01.009 · Cited by 80
Eleftheriou, A., Yoshida, M., & Henderson, B. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102656200 · Cited by 74
Zhang, F., White, R. L., & Neufeld, K. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.23.8143-8156.2001 · Cited by 73
Kawada, M., Seno, H., Uenoyama, Y., Sawabu, T., Kanda, N., Fukui, H., Shimahara, Y., & Chiba, T. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3460 · Cited by 73
“Other molecules, APC and lymphoid enhancer binding factor (LEF)-1, shuttle h-catenin between the cytoplasm and nucleus (18, 19).”
BackgroundInhibition of the Wnt Signaling Pathway by the PR61 Subunit of Protein Phosphatase 2A
Yamamoto, H., Hinoi, T., Michiue, T., Fukui, A., Usui, H., Janssens, V., HOOF, C. V., Goris, J., Asashima, M., & Kikuchi, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100443200 · Cited by 72
Chen, S., Wulf, G. M., Zhou, X. Z., Rubin, M. A., Lu, K. P., & Balk, S. P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.3.929-939.2006 · Cited by 72
Kuraguchi, M., Yang, K., Wong, E., Avdievich, E., Fan, K., Kolodner, R. D., Lipkin, M., Brown, A. M. C., Kucherlapati, R., & Edelmann, W. (2001) · PubMed · Cited by 72
Kadoya, T., Yamamoto, H., Suzuki, T., Yukita, A., Fukui, A., Michiue, T., Asahara, T., Tanaka, K., Asashima, M., & Kikuchi, A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.11.3803-3819.2002 · Cited by 71
“GFP–Axam-(1-113) was localized in the nucleus,”
BackgroundMethodInfluentialOct‐3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β‐catenin signalling
Abu-Remaileh, M., Gerson, A., Farago, M., Nathan, G., Alkalay, I., Rousso, S. Z., Gur, M., Fainsod, A., & Bergman, Y. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.200 · Cited by 72
“To investigate whether Oct-3/4 leads to b-catenin sub-cellular redistribution, similarly to Axin or APC (Henderson, 2000; Rosin-Arbesfeld et al, 2000; Cong and Varmus, 2004), or promotes b-catenin degradation in the nucleus, ZHBTc4 ES cells were treated with LMB, a highly specific inhibitor of the…”
BackgroundAPC, β-Catenin and hTCF-4; an unholy trinity in the genesis of colorectal cancer
Bright-Thomas, R., & Hargest, R. (2003) · European Journal of Surgical Oncology · doi:10.1053/ejso.2002.1331 · Cited by 68
β-Catenin mutations in sporadic fundic gland polyps
Sekine, S., Shibata, T., Yamauchi, Y., Nakanishi, Y., Shimoda, T., Sakamoto, M., & Hirohashi, S. (2001) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280100527 · Cited by 68
A novel function of adenomatous polyposis coli (APC) in regulating DNA repair
Jaiswal, A. S., & Narayan, S. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.06.024 · Cited by 67
“The APC gene product is a 310-kDa-homodimeric protein, which is localized in the cytoplasm and the nucleus [1], [2], [3], [4], [5], [6] and [7].”
Gao, X., Wen, J., Zhang, L., Li, X., Ning, Y., Meng, A., & Chen, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804088200 · Cited by 68
Bai, Y., Sha, J., & Kanno, T. (2020) · Cancers · doi:10.3390/cancers12030555 · Cited by 68
Controlling Protein Compartmentalization to Overcome Disease
Davis, J. R., Kakar, M., & Lim, C. S. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9133-z · Cited by 65
Ishiguro, H., Tsunoda, T., Tanaka, T., Fujii, Y., Nakamura, Y., & Furukawa, Y. (2001) · Oncogene · doi:10.1038/sj.onc.1204603 · Cited by 65
Mendoza-Topaz, C., Mieszczanek, J., & Bienz, M. (2011) · Open Biology · doi:10.1098/rsob.110013 · Cited by 67
“Similar results were obtained with HC, a minimal Axinbinding fragment from the central third of APC that is fully active in complementation assays of APC mutant colorectal cancer cells [38].”
BackgroundMethodResultInfluentialSelf-citationIdentification of Tcf-4 as a transcriptional target of p53 signalling
Rother, K., Johne, C., Spiesbach, K., Haugwitz, U., Tschöp, K., Wasner, M., Klein‐Hitpaß, L., Möröy, T., Mössner, J., & Engeland, K. (2004) · Oncogene · doi:10.1038/sj.onc.1207464 · Cited by 65
Jiao, W., Datta, J., Lin, H., Dundr, M., & Rane, S. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605271200 · Cited by 63
Everly, D. N., Kusano, S., & Raab‐Traub, N. (2004) · Journal of Virology · doi:10.1128/jvi.78.21.11648-11655.2004 · Cited by 62
“-Catenin import into and export from the nucleus is a regulated process (8, 16, 38).”
BackgroundReinacher‐Schick, A., & Gumbiner, B. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.491 · Cited by 62
“Also, the relationship of the 60S and/or membrane pool to the recently described nuclear export function of APC is not yet known (Henderson, 2000; Rosin-Arbesfeld et al., 2000).”
BackgroundStructural Basis of Targeting the Exportin CRM1 in Cancer
Dickmanns, A., Monecke, T., & Ficner, R. (2015) · Cells · doi:10.3390/cells4030538 · Cited by 61
“In non-transformed cells, APC is found in the nucleus and the cytoplasm, albeit with a more pronounced accumulation in the cytoplasm, as it bears both import and export signals [17,18].”
BackgroundInfluentialAdenomatous polyposis coli (Apc) tumor suppressor gene as a multifunctional gene
Senda, T., Shimomura, A., & Iizuka‐Kogo, A. (2005) · Anatomical Science International · doi:10.1111/j.1447-073x.2005.00106.x · Cited by 61
Vécsey-Semjén, B., Becker, K., Sinski, A., Blennow, E., Vietor, I., Zatloukal, K., Beug, H., Wagner, E., & Huber, L. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205577 · Cited by 60
“According to a current model, APC binds b-catenin, exports it from the nucleus (Henderson, 2000; Rosin-Arbesfeld et al., 2000) and targets it for phosphorylation within a protein complex consisting of APC, axin and glycogen synthase kinase 3b (GSK-3b).”
BackgroundMissing Links in GSK3 Regulation
Dominguez, I. M., & Green, J. B. A. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0317 · Cited by 60
“APC contains nuclear export sequences that seem to be important in its tumorsuppressing activity and reducing levels of nuclear b-catenin (Henderson, 2000; Rosin-Arbesfeld et al., 2000).”
BackgroundNucleocytoplasmic trafficking and transcription effects of huntingtin in Huntington's disease
Truant, R., Atwal, R. S., & Burtnik, A. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.11.004 · Cited by 59
Redefining the subcellular location and transport of APC: new insights using a panel of antibodies
Brocardo, M. G., Näthke, I. S., & Henderson, B. R. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400329 · Cited by 59
“APC can shuttle between the nucleus and cytoplasm (Henderson, 2000; Neufeld et al, 2000; Rosin-Arbesfeld et al, 2000), and its nuclear export may affect b-catenin localization and turnover (Henderson & Fagotto, 2002).”
BackgroundSchmitz, Y., Rateitschak, K., & Olaf Wolkenhauer, A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.07.005 · Cited by 58
Wnt signaling: the good and the bad
Chen, X., Yang, J., Evans, P. M., & Liu, C. (2008) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2008.00440.x · Cited by 56
Kohler, E. M., Derungs, A., Daum, G., Behrens, J., & Schneikert, J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn095 · Cited by 64
“A nuclear export signal (NES) located within the phosphorylatable region of the 20R3 between positions 1505 and 1512 has been previously described (43).”
BackgroundChan, S.-K., & Struhl, G. (2002) · Cell · doi:10.1016/s0092-8674(02)01037-1 · Cited by 58
RetractedAceto, G. M., Catalano, T., & Curia, M. C. (2020) · BioMed Research International · doi:10.1155/2020/1726309 · Cited by 60
“It might be possible according to the theory called “just-right nuclear export activity” that the loss of the central nuclear export signals—adjacent to the MCR region—has reduced nuclear export activity that compromises APC tumor-suppressing function [180, 181].”
BackgroundTownsley, F. M., & Bienz, M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00770-3 · Cited by 57
Self-citationClements, W. M., Lowy, A. M., & Groden, J. L. (2003) · Clinical Colorectal Cancer · doi:10.3816/ccc.2003.n.018 · Cited by 55
Matthaios, D., Balgkouranidou, I., Karayiannakis, A. J., Bolanaki, H., Xenidis, N., Amarantidis, K., Chelis, L., Romanidis, Κ., Chatzaki, Ε., Lianidou, E. S., et al. (2016) · Oncology Letters · doi:10.3892/ol.2016.4649 · Cited by 55
“Wild-type APC protein contributes to the destabilization and degradation of β -catenin, which is a central effector molecule in the Wnt/ β -catenin signaling pathway (22).”
Regulation of β‐Catenin Nuclear Dynamics by GSK‐3β Involves a LEF‐1 Positive Feedback Loop
Jamieson, C., Sharma, M., & Henderson, B. R. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01207.x · Cited by 52
Spears, E., & Neufeld, K. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.205922 · Cited by 53
Sànchez‐Tilló, E., de Barrios, O., Valls, E., Darling, D. S., Castells, A., & Postigo, A. A. (2015) · Oncogene · doi:10.1038/onc.2015.352 · Cited by 53
Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
Goh, Y., Cinghu, S., Hong, E. T. H., Lee, Y., Kim, J., Jang, J., Li, Y., Chi, X., Lee, K., Wee, H., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.071381 · Cited by 53
Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis
Coletta, P. L., Müller, A. M., Jones, E., Mühl, B., Holwell, S. E., Clarke, D., Meade, J. L., Cook, G. P., Hawcroft, G., Ponchel, F., et al. (2003) · Blood · doi:10.1182/blood-2003-03-0707 · Cited by 53
Nuclear-Cytoplasmic Shuttling of Chibby Controls β-Catenin Signaling
Li, F., Mofunanya, A., Fischer, V., Hall, J. C., & Takemaru, K. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-05-0437 · Cited by 52
“…Cby-14-3-3 pathway, the negative regulators of -catenin, APC and Axin, have been shown to shuttle between the nucleus and cytoplasm, and facilitate nuclear export of -catenin in a CRM1-dependent manner (Henderson, 2000; Rosin-Arbesfeld et al., 2000; Cong and Varmus, 2004; Wiechens et al., 2004).”
BackgroundRegulation of Wnt receptor activity: Implications for therapeutic development in colon cancer
Zhong, Z. A., Michalski, M. N., Stevens, P. D., Sall, E. A., & Williams, B. O. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100782 · Cited by 49
Qian, J., Sarnaik, A. A., Bonney, T. M., Keirsey, J. K., Combs, K. A., Steigerwald, K., Acharya, S., Behbehani, G. K., Barton, M. C., Lowy, A. M., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.074 · Cited by 48
Jiao, W., Lin, H.-M., Datta, J., Braunschweig, T. A., Chung, J.-Y., Hewitt, S. M., & Rane, S. G. (2007) · Oncogene · doi:10.1038/sj.onc.1210970 · Cited by 52
“…proteins APC, p53, p27Kip1and Smad4 (DPC4) can be inactivated by nuclear export mechanisms (Boyd et al., 2000; Geyer et al., 2000; Henderson, 2000; Rosin-Arbesfeld et al., 2000; Blain and Massague, 2002; Inman et al., 2002; Kastan and Zambetti, 2003; Xu and Massague, 2004; Ziegler and Ghosh,…”
BackgroundInfluentialJaiswal, A. S., & Narayan, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101298200 · Cited by 50
TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells
Vietor, I., Vadivelu, S. K., Wick, N., Hoffman, R. M., Cotten, M. L., Seiser, C., Fialka, I., Wunderlich, W., Haase, A. D. D., Kořínková, G., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf461 · Cited by 48
Li, N., Li, D., Du, Y., Chen, S., Yang, C., Lin, C., Li, X., & Hu, G. M. (2018) · Oncology Reports · doi:10.3892/or.2018.6914 · Cited by 46
“The activation of these downstream genes can promote the development of colorectal cancer (23-26).”
Cui, Y., Wu, X., Lin, C., Zhang, X., Ye, L., Ren, L., Chen, M., Yang, M., Li, Y., Li, M., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0807-5 · Cited by 47
β-catenin and its regulatory network
Klymkowsky, M. W. (2005) · Human Pathology · doi:10.1016/j.humpath.2005.02.002 · Cited by 46
Nuclear Functions for Plasma Membrane‐Associated Proteins?
Benmerah, A., Scott, M. G. H., Poupon, V., & Marullo, S. (2003) · Traffic · doi:10.1034/j.1600-0854.2003.00102.x · Cited by 46
Actin nucleators in the nucleus: an emerging theme
Weston, L., Coutts, A. S., & Thangue, N. B. L. (2012) · Journal of Cell Science · doi:10.1242/jcs.099523 · Cited by 45
“Nuclear APC has been shown to affect the Wnt signalling pathway by promoting both the sequestration and nuclear export of b-catenin (Henderson, 2000; Neufeld et al., 2000b; Rosin-Arbesfeld et al., 2000).”
BackgroundSiriwardena, B. S. M. S., Kudo, Y., Ogawa, I., Tilakaratne, W. M., & Takata, T. (2008) · Oral Oncology · doi:10.1016/j.oraloncology.2008.03.008 · Cited by 44
Mills, K. M., Brocardo, M. G., & Henderson, B. R. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-09-0632 · Cited by 44
Yang, L., Chen, H., Zhao, M., & Peng, P. (2017) · Oncotarget · doi:10.18632/oncotarget.16597 · Cited by 43
“Oncotarget40217www.impactjournals.com/oncotarget by stimulating β-catenin-TCF-4 target gene [27, 28] and inducing E-cadherin [29, 30].”
BackgroundLin, Y. M., Ono, K., Satoh, S., Ishiguro, H., Fujita, M., Miwa, N., Tanaka, T., Tsunoda, T., Yang, K.-X., Nakamura, Y., et al. (2001) · PubMed · Cited by 43
Zhang, Y., Qiu, W.-J., Liu, D., Neo, S. Y., He, X., & Lin, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104451200 · Cited by 43
Kressel, M. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.19.2269 · Cited by 42
“APC is able to enter the cell nucleus and this ability is critical for its tumor suppressor function (50).”
BackgroundProtein 4.1-mediated Membrane Targeting of Human Discs Large in Epithelial Cells
Hanada, T., Takeuchi, A., Sondarva, G. V., & Chishti, A. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305209200 · Cited by 42
Brocardo, M. G., Lei, Y., Tighe, A., Taylor, S. S., Mok, M. T. S., & Henderson, B. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708775200 · Cited by 42
Li, Z., & Näthke, I. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4609 · Cited by 40
Galea, M. A., Eleftheriou, A., & Henderson, B. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107149200 · Cited by 41
Choi, J., Park, S. Y., Costantini, F. D., Jho, E., & Joo, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404655200 · Cited by 41
A Markov Chain Model of the B-Cell Algorithm
Clark, E., Hone, A. N. W., & Timmis, J. (2005) · Lecture notes in computer science · doi:10.1007/11536444_24 · Cited by 41
“Evidence of an analogous biological mechanism in the immunological literature is sparse [3], however, the authors do argue that mutation occurs in clusters of regions within cells: this is broadly analogous to contiguous regions.”
BackgroundHenderson, B. R., Galea, M. A., Schüchner, S., & Leung, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110602200 · Cited by 41
Metadata
- Authors
- Rosin-Arbesfeld, R., Townsley, F., & Bienz, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Bienz, Mariann
- ORCID
- Bienz, Mariann
- Venue
- Nature
- Published
- 2000-08
- Volume
- 406
- Issue
- 6799
- Pages
- 1009-1012
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1666932156
- Cited by
- 343
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 10
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- nuclear export, nuclear export signal, β-catenin stabilization, colorectal cancer, proteasomal degradation, armadillos, mutation cluster region, tumor suppressor function
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Cell Nucleus, Cytoskeletal Proteins, Drosophila, Fatty Acids, Unsaturated, Multigene Family, Genetic Complementation Test, Humans, Molecular Sequence Data, Mutation, Peptide Fragments, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Colorectal Neoplasms, Trans-Activators, Conserved Sequence, Genes, Reporter, COS Cells, Adenomatous Polyposis Coli Protein, beta Catenin
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
