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http://dx.doi.org/10.4014/kjmb.1402.02001

Suppression of the Wnt/${\beta}$-catenin Pathway by Bryostatin-1  

Park, Seoyoung (Department of Bio and Fermentation Convergence Technology, Kookmin University)
Oh, Sangtaek (Department of Bio and Fermentation Convergence Technology, Kookmin University)
Publication Information
Microbiology and Biotechnology Letters / v.42, no.1, 2014 , pp. 89-92 More about this Journal
Abstract
The Wnt/${\beta}$-catenin pathway plays important roles in a variety of biological processes, such as cell proliferation, differentiation, and organ development. Here, we used a cell-based reporter assay to identify bryostatin-1, a natural macrocyclic lactone, as an inhibitor of the Wnt/${\beta}$-catenin pathway. Bryostatin-1 suppressed ${\beta}$-catenin response transcription (CRT), which was activated by a Wnt3a-conditioned medium (Wnt3a-CM), through a decrease in the intracellular ${\beta}$-catenin protein levels, without affecting its mRNA level. In addition, pharmacological inhibition of proteasome abrogated bryostatin-1-mediated down-regulation of the ${\beta}$-catenin protein level. Our findings suggest that bryostatin-1 attenuates the Wnt/${\beta}$-catenin pathway through the promotion of proteasomal degradation of ${\beta}$-catenin.
Keywords
Wnt/${\beta}$-catenin pathway; bryostatin-1; protein degradation;
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1 Morin PJ. 1999. $\beta$-catenin signaling and cancer. Bioessays 21: 1021-1030.   DOI   ScienceOn
2 Matsuzawa SI, Reed JC. 2001. Siah-1, SIP, and Ebi collaborate in a novel pathway for $\beta$-catenin degradation linked to p53 responses. Mol. Cell 7: 915-926.   DOI   ScienceOn
3 Miller JR. 2002. The Wnts. Genome Biol. 3: reviews3001.1- reviews3001.15.
4 Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. 1997. Activation of $\beta$-catenin-Tcf signaling in colon cancer by mutations in $\beta$-catenin or APC. Science 275: 1787-1790.   DOI   ScienceOn
5 Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW. 1997. Serine phosphorylation-regulated ubquitination and degradation of $\beta$-catenin. J. Biol. Chem. 272: 24735-24738.   DOI
6 Pettit GR, Herald CL, Doubek DL, Herald DL, Arnold E, Clardy J. 1982. Isolation and structure of bryostatin 1. J. Am. Chem. Soc. 104: 6846-6848.   DOI
7 Polakis P. 2002. Casein kinase 1: a Wnt'er of disconnect. Curr. Biol. 12: R499-R501.   DOI   ScienceOn
8 Shaha SP, Tomic J, Shi Y, Pham T, Mero P, White D, et al. 2009. Prolonging microtubule dysruption enhances the immunogenicity of chronic lymphocytic leukaemia cells. Clin. Exp. Immunol. 158: 186-198.   DOI
9 Sun MK, Alkon DL. 2005. Dual effects of bryostatin-1 on spatial memory and depression. Eur. J. Pharm. 512: 43-51.   DOI
10 Takahashi M, Tsunoda T, Seiki M, Nakamura Y, Furukawa Y. 2002. Identification of membrane-type matrix metalloproteinase- 1 as a target of the $\beta$-catenin/Tcf4 complex in human colorectal cancers. Oncogene 21: 5861-5867.   DOI   ScienceOn
11 Tetsu O, McCormick F. 1999. $\beta$-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398: 422-426.   DOI   ScienceOn
12 Hale KJ, Hummersone MG, Manaviazar S, Frigerio M. 2002. The chemistry and biology of the bryostatin antitumour macrolides. Nat. Prod. Rep. 19: 413-453.   DOI
13 Dignam JD, Lebovitz RM, Roeder RG. 1983. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11: 1475- 1489.   DOI   ScienceOn
14 Fearnhead NS, Britton MP, Bodmer WF. 2001. The ABC of APC. Hum. Mol. Genet. 10: 721-733.   DOI   ScienceOn
15 Giles RH, van Es JH, Clevers H. 2003. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta. 1653: 1-24.
16 He TC, Chan TA, Vogelstein B, Kinzler KW. 1999. PPARO is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99: 335-345.   DOI   ScienceOn
17 He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. 1998. Identification of c-MYC as a target of the APC pathway. Science 281: 1509- 1512.   DOI   ScienceOn
18 Jaggi M, Chauhan SC, Du C, Balaji KC. 2008. Bryostatin 1 modulates $\beta$-catenin subcellular localization and transcription activity through protein kinase D1 activation. Mol. Cancer Ther. 7: 2703-271.   DOI
19 Karim R, Tse G, Putti T, Scolyer R, Lee S. 2004. The significance of the Wnt pathway in the pathology of human cancers. Pathology 36: 120-128.   DOI
20 Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. 1997. Constitutive transcriptional activation by a $\beta$-catenin-Tcf complex in APC -/- colon carcinoma. Science 275: 1784-1787.   DOI   ScienceOn
21 Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW. 2003. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol. 1: 116-132.
22 Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, et al. 2001. Siah-1 mediates a novel $\beta$-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol. Cell 7: 927-936.   DOI   ScienceOn
23 Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. 1997. $\beta$- Catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 16: 3797-3804.   DOI   ScienceOn