This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shtutman, M. Articles by Ben-Ze’ev, A. Search for Related Content PubMed PubMed Citation Articles by Shtutman, M. Articles by Ben-Ze’ev, A.

PML Is a Target Gene of ß-Catenin and Plakoglobin, and Coactivates ß-Catenin-mediated Transcription¹

Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

ß-Catenin and its close homologue plakoglobin (-catenin) are major constituents of submembranal cell-cell adhesion sites. In addition, ß-catenin is a key component in the canonical Wnt pathway. Aberrantly activated ß-catenin signaling contributes to cancer progression by inducing [in complex with lymphocyte enhancer factor (LEF)/T-cell factor (TCF)] the transcription of proliferation-related genes such as cyclin D1 and c-myc. Plakoglobin can also activate LEF/TCF-mediated transcription. Excessive ß-catenin signaling in MEF triggers a p53-mediated antiproliferative response by inducing the expression of ARF. We have demonstrated previously that plakoglobin also exerts a tumor-suppressive effect in certain cancer cell lines. To identify genes induced by ß-catenin and plakoglobin, DNA microarray analysis was carried out, and PML was among those genes of which the expression was significantly elevated by both plakoglobin and ß-catenin. Activation of the PML promoter by ß-catenin and plakoglobin was LEF/TCF-independent. We found that PML forms a complex with ß-catenin in cells, and the two proteins colocalize in the nucleus. In addition, PML, p300, and ß-catenin cooperated in transactivation of a subset of ß-catenin-responsive genes including ARF and Siamois but not cyclin D1. Retroviral expression of ß-catenin, plakoglobin, or PML suppressed the tumorigenicity of p53-negative human renal carcinoma cells, thus pointing to a novel antioncogenic response triggered by catenins that is mediated by the induction of PML.

This article has been cited by other articles:

				P. D. McCrea, D. Gu, and M. S. Balda Junctional Music that the Nucleus Hears: Cell-Cell Contact Signaling and the Modulation of Gene Activity Cold Spring Harb Perspect Biol, October 1, 2009; 1(4): a002923 - a002923. [Abstract] [Full Text] [PDF]

				M. Saegusa, M. Hashimura, T. Kuwata, M. Hamano, Y. Wani, and I. Okayasu A functional role of Cdx2 in {beta}-catenin signaling during transdifferentiation in endometrial carcinomas Carcinogenesis, September 1, 2007; 28(9): 1885 - 1892. [Abstract] [Full Text] [PDF]

				Z. Den, X. Cheng, M. Merched-Sauvage, and P. J. Koch Desmocollin 3 is required for pre-implantation development of the mouse embryo J. Cell Sci., February 1, 2006; 119(3): 482 - 489. [Abstract] [Full Text] [PDF]

				I. Lassot, E. Estrabaud, S. Emiliani, M. Benkirane, R. Benarous, and F. Margottin-Goguet p300 Modulates ATF4 Stability and Transcriptional Activity Independently of Its Acetyltransferase Domain J. Biol. Chem., December 16, 2005; 280(50): 41537 - 41545. [Abstract] [Full Text] [PDF]

				S. Dihlmann, M. Kloor, C. Fallsehr, and M. von Knebel Doeberitz Regulation of AKT1 expression by beta-catenin/Tcf/Lef signaling in colorectal cancer cells Carcinogenesis, September 1, 2005; 26(9): 1503 - 1512. [Abstract] [Full Text] [PDF]

				Y. Shav-Tal, J. Blechman, X. Darzacq, C. Montagna, B. T. Dye, J. G. Patton, R. H. Singer, and D. Zipori Dynamic Sorting of Nuclear Components into Distinct Nucleolar Caps during Transcriptional Inhibition Mol. Biol. Cell, May 1, 2005; 16(5): 2395 - 2413. [Abstract] [Full Text] [PDF]

				C. Labalette, C.-A. Renard, C. Neuveut, M.-A. Buendia, and Y. Wei Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and {beta}-Catenin Mol. Cell. Biol., December 15, 2004; 24(24): 10689 - 10702. [Abstract] [Full Text] [PDF]

				J. Hulit, C. Wang, Z. Li, C. Albanese, M. Rao, D. Di Vizio, S. Shah, S. W. Byers, R. Mahmood, L. H. Augenlicht, et al. Cyclin D1 Genetic Heterozygosity Regulates Colonic Epithelial Cell Differentiation and Tumor Number in ApcMin Mice Mol. Cell. Biol., September 1, 2004; 24(17): 7598 - 7611. [Abstract] [Full Text] [PDF]

				M. Saegusa, M. Hashimura, T. Kuwata, M. Hamano, and I. Okayasu {beta}-Catenin Simultaneously Induces Activation of the p53-p21WAF1 Pathway and Overexpression of Cyclin D1 during Squamous Differentiation of Endometrial Carcinoma Cells Am. J. Pathol., May 1, 2004; 164(5): 1739 - 1749. [Abstract] [Full Text] [PDF]

				C. Muller-Tidow, B. Steffen, T. Cauvet, L. Tickenbrock, P. Ji, S. Diederichs, B. Sargin, G. Kohler, M. Stelljes, E. Puccetti, et al. Translocation Products in Acute Myeloid Leukemia Activate the Wnt Signaling Pathway in Hematopoietic Cells Mol. Cell. Biol., April 1, 2004; 24(7): 2890 - 2904. [Abstract] [Full Text] [PDF]

				T. Sekiya, S. Adachi, K. Kohu, T. Yamada, O. Higuchi, Y. Furukawa, Y. Nakamura, T. Nakamura, K. Tashiro, S. Kuhara, et al. Identification of BMP and Activin Membrane-bound Inhibitor (BAMBI), an Inhibitor of Transforming Growth Factor-{beta} Signaling, as a Target of the {beta}-Catenin Pathway in Colorectal Tumor Cells J. Biol. Chem., February 20, 2004; 279(8): 6840 - 6846. [Abstract] [Full Text] [PDF]

				O. Larsson, C. Scheele, Z. Liang, J. Moll, C. Karlsson, and C. Wahlestedt Kinetics of Senescence-associated Changes of Gene Expression in an Epithelial, Temperature-sensitive SV40 Large T Antigen Model Cancer Res., January 15, 2004; 64(2): 482 - 489. [Abstract] [Full Text] [PDF]

				I. Louria-Hayon, T. Grossman, R. V. Sionov, O. Alsheich, P. P. Pandolfi, and Y. Haupt The Promyelocytic Leukemia Protein Protects p53 from Mdm2-mediated Inhibition and Degradation J. Biol. Chem., August 29, 2003; 278(35): 33134 - 33141. [Abstract] [Full Text] [PDF]