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Science 4 September 1998:
Vol. 281. no. 5382, pp. 1509 - 1512
DOI: 10.1126/science.281.5382.1509
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Reports

Identification of c-MYC as a Target of the APC Pathway

Tong-Chuan He, Andrew B. Sparks, Carlo Rago, Heiko Hermeking, Leigh Zawel, Luis T. da Costa, Patrice J. Morin, Bert Vogelstein, Kenneth W. Kinzler *

The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of beta -catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by beta -catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.

T.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USA.
*   To whom correspondence should be addressed. E-mail: kinzlke{at}welchlink.welch.jhu.edu

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Development 135, 1875-1885
   Abstract »    Full Text »    PDF »
HDAC6 Is Required for Epidermal Growth Factor-induced {beta}-Catenin Nuclear Localization.
Y. Li, X. Zhang, R. D. Polakiewicz, T.-P. Yao, and M. J. Comb (2008)
J. Biol. Chem. 283, 12686-12690
   Abstract »    Full Text »    PDF »
Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3{beta} Inactivation.
T. M. Thornton, G. Pedraza-Alva, B. Deng, C. D. Wood, A. Aronshtam, J. L. Clements, G. Sabio, R. J. Davis, D. E. Matthews, B. Doble, et al. (2008)
Science 320, 667-670
   Abstract »    Full Text »    PDF »
Cooperative Control via Lymphoid Enhancer Factor 1/T Cell Factor 3 and Estrogen Receptor-{alpha} for Uterine Gene Regulation by Estrogen.
S. Ray, F. Xu, H. Wang, and S. K. Das (2008)
Mol. Endocrinol. 22, 1125-1140
   Abstract »    Full Text »    PDF »
Cross Talk between the Insulin and Wnt Signaling Pathways: Evidence from Intestinal Endocrine L Cells.
F. Yi, J. Sun, G. E. Lim, I. G. Fantus, P. L. Brubaker, and T. Jin (2008)
Endocrinology 149, 2341-2351
   Abstract »    Full Text »    PDF »
Epigenetic inactivation of the secreted frizzled-related protein-5 (SFRP5) gene in human breast cancer is associated with unfavorable prognosis.
J. Veeck, C. Geisler, E. Noetzel, S. Alkaya, A. Hartmann, R. Knuchel, and E. Dahl (2008)
Carcinogenesis 29, 991-998
   Abstract »    Full Text »    PDF »
{alpha}E-catenin is not a significant regulator of {beta}-catenin signaling in the developing mammalian brain.
W.-H. Lien, O. Klezovitch, M. Null, and V. Vasioukhin (2008)
J. Cell Sci. 121, 1357-1362
   Abstract »    Full Text »    PDF »
Genome-Wide Pattern of TCF7L2/TCF4 Chromatin Occupancy in Colorectal Cancer Cells.
P. Hatzis, L. G. van der Flier, M. A. van Driel, V. Guryev, F. Nielsen, S. Denissov, I. J. Nijman, J. Koster, E. E. Santo, W. Welboren, et al. (2008)
Mol. Cell. Biol. 28, 2732-2744
   Abstract »    Full Text »    PDF »
Nuclear Dvl, c-Jun, {beta}-catenin, and TCF form a complex leading to stabiLization of {beta}-catenin-TCF interaction.
X.-q. Gan, J.-y. Wang, Y. Xi, Z.-l. Wu, Y.-p. Li, and L. Li (2008)
J. Cell Biol. 180, 1087-1100
   Abstract »    Full Text »    PDF »
A novel role for Lef-1, a central transcription mediator of Wnt signaling, in leukemogenesis.
K. Petropoulos, N. Arseni, C. Schessl, C. R. Stadler, V. P.S. Rawat, A. J. Deshpande, B. Heilmeier, W. Hiddemann, L. Quintanilla-Martinez, S. K. Bohlander, et al. (2008)
J. Exp. Med. 205, 515-522
   Abstract »    Full Text »    PDF »
Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells.
M. F. Cole, S. E. Johnstone, J. J. Newman, M. H. Kagey, and R. A. Young (2008)
Genes & Dev. 22, 746-755
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{beta}-Catenin Expression Results in p53-Independent DNA Damage and Oncogene-Induced Senescence in Prelymphomagenic Thymocytes In Vivo.
M. Xu, Q. Yu, R. Subrahmanyam, M. J. Difilippantonio, T. Ried, and J. M. Sen (2008)
Mol. Cell. Biol. 28, 1713-1723
   Abstract »    Full Text »    PDF »
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.
H. Tran, F. Hamada, T. Schwarz-Romond, and M. Bienz (2008)
Genes & Dev. 22, 528-542
   Abstract »    Full Text »    PDF »
Inactivation of nuclear Wnt-{beta}-catenin signaling limits blastocyst competency for implantation.
H. Xie, S. Tranguch, X. Jia, H. Zhang, S. K. Das, S. K. Dey, C. J. Kuo, and H. Wang (2008)
Development 135, 717-727
   Abstract »    Full Text »    PDF »
Suppressor role of activating transcription factor 2 (ATF2) in skin cancer.
A. Bhoumik, B. Fichtman, C. DeRossi, W. Breitwieser, H. M. Kluger, S. Davis, A. Subtil, P. Meltzer, S. Krajewski, N. Jones, et al. (2008)
PNAS 105, 1674-1679
   Abstract »    Full Text »    PDF »


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