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Journal of Signal Transduction
Volume 2012 (2012), Article ID 294097, 10 pages
http://dx.doi.org/10.1155/2012/294097
Review Article

Crosstalk between p53 and TGF- 𝜷 Signalling

Division of Cancer Research, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK

Received 30 September 2011; Accepted 11 November 2011

Academic Editor: Herman P. Spaink

Copyright © 2012 Rebecca Elston and Gareth J. Inman. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Massagué, “TGFβ in cancer,” Cell, vol. 134, no. 2, pp. 215–230, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. R. Derynck and Y. E. Zhang, “Smad-dependent and Smad-independent pathways in TGF-β family signalling,” Nature, vol. 425, no. 6958, pp. 577–584, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. R. L. Elliott and G. C. Blobe, “Role of transforming growth factor β in human cancer,” Journal of Clinical Oncology, vol. 23, no. 9, pp. 2078–2093, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. H. Ikushima and K. Miyazono, “TGFβ singalling: a complex web in cancer progression,” Nature Reviews Cancer, vol. 10, no. 6, pp. 415–424, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. Y. Shi and J. Massagué, “Mechanisms of TGF—β signaling from cell membrane to the nucleus,” Cell, vol. 113, no. 6, pp. 685–700, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. P. M. Siegel and J. Massagué, “Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer,” Nature Reviews Cancer, vol. 3, no. 11, pp. 807–821, 2003. View at Scopus
  7. B. Bierie and H. L. Moses, “Tumour microenvironment: TGFβ: the molecular Jekyll and Hyde of cancer,” Nature Reviews Cancer, vol. 6, no. 7, pp. 506–520, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. C. H. Heldin, M. Landstrom, and A. Moustakas, “Mechanism of TGF-β signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition,” Current Opinion in Cell Biology, vol. 21, no. 2, pp. 166–176, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. L. Levy and C. S. Hill, “Alterations in components of the TGF-β superfamily signaling pathways in human cancer,” Cytokine and Growth Factor Reviews, vol. 17, no. 1-2, pp. 41–58, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. A. B. Roberts and L. M. Wakefield, “The two faces of transforming growth factor β in carcinogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8621–8623, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. E. Meulmeester and P. T. Dijke, “The dynamic roles of TGF-β in cancer,” Journal of Pathology, vol. 223, no. 2, pp. 205–218, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. G. J. Inman, “Switching TGFβ from a tumor suppressor to a tumor promoter,” Current Opinion in Genetics & Development, vol. 21, no. 1, pp. 93–99, 2011.
  13. T. Huang, L. David, V. Mendoza, et al., “TGF-β signalling is mediated by two autonomously functioning TβRI: TβRII pairs,” The EMBO Journal, vol. 30, no. 7, pp. 1263–1276, 2011. View at Publisher · View at Google Scholar · View at PubMed
  14. J. Massagué, “A very private TGF-β receptor embrace,” Molecular Cell, vol. 29, no. 2, pp. 149–150, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. J. Groppe, C. S. Hinck, P. Samavarchi-Tehrani et al., “Cooperative assembly of TGF-β superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding,” Molecular Cell, vol. 29, no. 2, pp. 157–168, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. J. Massagué, J. Seoane, and D. Wotton, “Smad transcription factors,” Genes and Development, vol. 19, no. 23, pp. 2783–2810, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. C. H. Heldin and A. Moustakas, “Role of Smads in TGFβ signaling,” Cell and Tissue Research, vol. 347, no. 1, pp. 21–26, 2012. View at Publisher · View at Google Scholar · View at PubMed
  18. X. H. Feng and R. Derynck, “Specificity and versatility in TGF-β signaling through smads,” Annual Review of Cell and Developmental Biology, vol. 21, pp. 659–693, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. S. Ramesh, X. J. Qi, G. M. Wildey et al., “TGFβ-mediated BIM expression and apoptosis are regulated through SMAD3-dependent expression of the MAPK phosphatase MKP2,” EMBO Reports, vol. 9, no. 10, pp. 990–997, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. L. C. Spender, D. I. O'Brien, D. Simpson et al., “TGF-β induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL,” Cell Death and Differentiation, vol. 16, no. 4, pp. 593–602, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. Y. Zhang, “Non-Smad pathways in TGF-β signaling,” Cell Research, vol. 19, no. 1, pp. 128–139, 2009. View at Publisher · View at Google Scholar · View at PubMed
  22. Y. Mu, S. K. Gudey, and M. Landstrom, “Non-Smad signaling pathways,” Cell and Tissue Research, vol. 347, no. 1, pp. 11–20, 2012. View at Publisher · View at Google Scholar · View at PubMed
  23. K. H. Vousden and C. Prives, “Blinded by the light: the growing complexity of p53,” Cell, vol. 137, no. 3, pp. 413–431, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. D. P. Lane, “p53, guardian of the genome,” Nature, vol. 358, no. 6381, pp. 15–16, 1992. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. A. J. Levine and M. Oren, “The first 30 years of p53: growing ever more complex,” Nature Reviews Cancer, vol. 9, no. 10, pp. 749–758, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. R. Beckerman and C. Prives, “Transcriptional regulation by p53,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 8, p. a000935, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. Y. Haupt, R. Maya, A. Kazaz, and M. Oren, “Mdm2 promotes the rapid degradation of p53,” Nature, vol. 387, no. 6630, pp. 296–299, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. M. H. Kubbutat, S. N. Jones, and K. H. Vousden, “Regulation of p53 stability by Mdm2,” Nature, vol. 387, no. 6630, pp. 299–303, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. Hock and K. H. Vousden, “Regulation of the p53 pathway by ubiquitin and related proteins,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 10, pp. 1618–1621, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. K. Nakano and K. H. Vousden, “PUMA, a novel proapoptotic gene, is induced by p53,” Molecular Cell, vol. 7, no. 3, pp. 683–694, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. J. Yu, L. Zhang, P. M. Hwang, K. W. Kinzler, and B. Vogelstein, “PUMA induces the rapid apoptosis of colorectal cancer cells,” Molecular Cell, vol. 7, no. 3, pp. 673–682, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. W. S. El-Deiry, T. Tokino, V. E. Velculescu et al., “WAF1, a potential mediator of p53 tumor suppression,” Cell, vol. 75, no. 4, pp. 817–825, 1993. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Oda, R. Ohki, H. Murasawa et al., “Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis,” Science, vol. 288, no. 5468, pp. 1053–1058, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. O. D. Maddocks and K. H. Vousden, “Metabolic regulation by p53,” Journal of Molecular Medicine, vol. 89, no. 3, pp. 237–245, 2011. View at Publisher · View at Google Scholar · View at PubMed
  35. T. Soussi, “TP53 mutations in human cancer: database reassessment and prospects for the next decade,” Advances in Cancer Research, vol. 110, pp. 107–139, 2011. View at Publisher · View at Google Scholar · View at PubMed
  36. A. M. Goh, C. R. Coffill, and D. P. Lane, “The role of mutant p53 in human cancer,” Journal of Pathology, vol. 223, no. 2, pp. 116–126, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Oren and V. Rotter, “Mutant p53 gain-of-function in cancer,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 2, p. a001107, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. H. Song, M. Hollstein, and Y. Xu, “p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM,” Nature Cell Biology, vol. 9, no. 5, pp. 573–580, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. Willis, E. J. Jung, T. Wakefield, and X. Chen, “Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes,” Oncogene, vol. 23, no. 13, pp. 2330–2338, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. L. Xu, Y. Kang, S. Col, and J. Massagué, “Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFβ signaling complexes in the cytoplasm and nucleus,” Molecular Cell, vol. 10, no. 2, pp. 271–282, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. G. J. Inman, F. J. Nicolas, and C. S. Hill, “Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-β receptor activity,” Molecular Cell, vol. 10, no. 2, pp. 283–294, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Ross and C. S. Hill, “How the Smads regulate transcription,” International Journal of Biochemistry and Cell Biology, vol. 40, no. 3, pp. 383–408, 2008. View at Publisher · View at Google Scholar · View at PubMed
  43. H. Ikushima and K. Miyazono, “Cellular context—dependent “colors” of transforming growth factor—β signaling,” Cancer Science, vol. 101, no. 2, pp. 306–312, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. C. Alarcon, A. I. Zaromytidou, Q. Xi et al., “Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways,” Cell, vol. 139, no. 4, pp. 757–769, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. I. Ringshausen, C. C. O'Shea, A. J. Finch, L. B. Swigart, and G. I. Evan, “Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo,” Cancer Cell, vol. 10, no. 6, pp. 501–514, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. M. Cordenonsi, M. Montagner, M. Adorno et al., “Integration of TGF-β and Ras/MAPK signaling through p53 phosphorylation,” Science, vol. 315, no. 5813, pp. 840–843, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. M. Cordenonsi, S. Dupont, S. Maretto, A. Insinga, C. Imbriano, and S. Piccolo, “Links between tumor suppressors: p53 is required for TGF-β gene responses by cooperating with Smads,” Cell, vol. 113, no. 3, pp. 301–314, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. S. Dupont, L. Zacchigna, M. Adorno et al., “Convergence of p53 and TGF-β signaling networks,” Cancer Letters, vol. 213, no. 2, pp. 129–138, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. B. N. Davis, A. C. Hilyard, G. Lagna, and A. Hata, “SMAD proteins control DROSHA-mediated microRNA maturation,” Nature, vol. 454, no. 7200, pp. 56–61, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. H. I. Suzuki, K. Yamagata, K. Sugimoto, T. Iwamoto, S. Kato, and K. Miyazono, “Modulation of microRNA processing by p53,” Nature, vol. 460, no. 7254, pp. 529–533, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. B. N. Davis, A. C. Hilyard, P. H. Nguyen, G. Lagna, and A. Hata, “Smad proteins bind a conserved RNA sequence to promote MicroRNA maturation by Drosha,” Molecular Cell, vol. 39, no. 3, pp. 373–384, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. D. R. Warner, V. Bhattacherjee, X. Yin et al., “Functional interaction between Smad, CREB binding protein, and p68 RNA helicase,” Biochemical and Biophysical Research Communications, vol. 324, no. 1, pp. 70–76, 2004. View at Publisher · View at Google Scholar · View at PubMed
  53. M. Adorno, M. Cordenonsi, M. Montagner et al., “A mutant-p53/Smad complex opposes p63 to empower TGFβ-induced metastasis,” Cell, vol. 137, no. 1, pp. 87–98, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. P. A. Muller, P. T. Caswell, B. Doyle et al., “Mutant p53 drives invasion by promoting integrin recycling,” Cell, vol. 139, no. 7, pp. 1327–1341, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. F. S. Wyllie, T. Dawson, J. Bond et al., “Correlated abnormalities of transforming growth factor-β1 response and p53 expression in thyroid epithelial cell transformation,” Molecular and Cellular Endocrinology, vol. 76, no. 1–3, pp. 13–21, 1991. View at Scopus
  56. K. Takebayashi-Suzuki, J. Funami, D. Tokumori et al., “Interplay between the tumor suppressor p53 and TGFβ signaling shapes embryonic body axes in Xenopus,” Development, vol. 130, no. 17, pp. 3929–3939, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. X. Chen, E. Weisberg, V. Fridmacher, M. Watanabe, G. Naco, and M. Whitman, “Smad4 and FAST-1 in the assembly of activin-responsive factor,” Nature, vol. 389, no. 6646, pp. 85–89, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. R. W. Carthew and E. J. Sontheimer, “Origins and mechanisms of miRNAs and siRNAs,” Cell, vol. 136, no. 4, pp. 642–655, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. M. Inui, G. Martello, and S. Piccolo, “MicroRNA control of signal transduction,” Nature Reviews Molecular Cell Biology, vol. 11, no. 4, pp. 252–263, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Lee, C. Ahn, J. Han et al., “The nuclear RNase III Drosha initiates microRNA processing,” Nature, vol. 425, no. 6956, pp. 415–419, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. R. S. Pillai, C. G. Artus, and W. Filipowicz, “Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis,” RNA, vol. 10, no. 10, pp. 1518–1525, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. M. S. Kumar, J. Lu, K. L. Mercer, T. R. Golub, and T. Jacks, “Impaired microRNA processing enhances cellular transformation and tumorigenesis,” Nature Genetics, vol. 39, no. 5, pp. 673–677, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. A. Esquela-Kerscher and F. J. Slack, “Oncomirs—MicroRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. H. I. Suzuki and K. Miyazono, “Dynamics of microRNA biogenesis: crosstalk between p53 network and microRNA processing pathway,” Journal of Molecular Medicine, vol. 88, no. 11, pp. 1085–1094, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. C. J. Braun, X. Zhang, I. Savelyeva et al., “p53-responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest,” Cancer Research, vol. 68, no. 24, pp. 10094–10104, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. S. A. Georges, M. C. Biery, S. Y. Kim et al., “Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215,” Cancer Research, vol. 68, no. 24, pp. 10105–10112, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob, and T. Patel, “MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer,” Gastroenterology, vol. 133, no. 2, pp. 647–658, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. C. Polytarchou, D. Iliopoulos, M. Hatziapostolou et al., “Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation,” Cancer Research, vol. 71, no. 13, pp. 4720–4731, 2011. View at Publisher · View at Google Scholar · View at PubMed
  71. T. Fukuda, K. Yamagata, S. Fujiyama et al., “DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs,” Nature Cell Biology, vol. 9, no. 5, pp. 604–611, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. E. Kalo, Y. Buganim, K. E. Shapira et al., “Mutant p53 attenuates the SMAD-dependent transforming growth factor β1 (TGF-β1) signaling pathway by repressing the expression of TGF-β receptor type II,” Molecular and Cellular Biology, vol. 27, no. 23, pp. 8228–8242, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. C. E. Wilkins-Port, Q. Ye, J. E. Mazurkiewicz, and P. J. Higgins, “TGF-β1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/mmp-10/mmp-1-dependent collagen remodeling axis: role for PAI-1,” Cancer Research, vol. 69, no. 9, pp. 4081–4091, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. D. Hanahan and R. A. Weinberg, “The hallmarks of cancer,” Cell, vol. 100, no. 1, pp. 57–70, 2000. View at Scopus
  75. A. Atfi and R. Baron, “p53 brings a new twist to the Smad signaling network,” Science Signaling, vol. 1, no. 26, p. pe33, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. W. S. El-Deiry, S. E. Kern, J. A. Pietenpol, K. W. Kinzler, and B. Vogelstein, “Definition of a consensus binding site for p53,” Nature Genetics, vol. 1, no. 1, pp. 45–49, 1992. View at Scopus
  77. D. C. Corney, A. Flesken-Nikitin, A. K. Godwin, W. Wang, and A. Y. Nikitin, “MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth,” Cancer Research, vol. 67, no. 18, pp. 8433–8438, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. D. S. Wilkinson, S. K. Ogden, S. A. Stratton et al., “A direct intersection between p53 and transforming growth factor β pathways targets chromatin modification and transcription repression of the α-fetoprotein gene,” Molecular and Cellular Biology, vol. 25, no. 3, pp. 1200–1212, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. K. Polyak and R. A. Weinberg, “Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits,” Nature Reviews Cancer, vol. 9, no. 4, pp. 265–273, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. M. P. Khoury and J. C. Bourdon, “The isoforms of the p53 protein,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 3, p. a000927, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. J. Lindsay, S. S. McDade, A. Pickard, K. D. McCloskey, and D. J. McCance, “Role of δNp63γ in epithelial to mesenchymal transition,” Journal of Biological Chemistry, vol. 286, no. 5, pp. 3915–3924, 2011. View at Publisher · View at Google Scholar · View at PubMed