| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell and Tumor Biology |
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
Requests for reprints: Donald Kufe, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3141; Fax: 617-632-2934; E-mail: donald_kufe{at}dfci.harvard.edu.
Dysregulation of ß-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with ß-catenin. However, the functional significance of the MUC1-ß-catenin interaction is not known. Here, we show that MUC1 increases ß-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3ß (GSK3ß) phosphorylates ß-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of ß-catenin levels, our results show that MUC1 blocks GSK3ß-mediated phosphorylation and degradation of ß-catenin. To further define the interaction between MUC1 and ß-catenin, we identified a serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to ß-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to ß-catenin and MUC1-mediated inhibition of ß-catenin degradation. Importantly, disruption of the MUC1-ß-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes transformation, at least in part, by blocking GSK3ß-mediated phosphorylation and thereby degradation of ß-catenin.
This article has been cited by other articles:
|
|
 |
|
  T. Kawano, M. Ito, D. Raina, Z. Wu, J. Rosenblatt, D. Avigan, R. Stone, and D. Kufe MUC1 Oncoprotein Regulates Bcr-Abl Stability and Pathogenesis in Chronic Myelogenous Leukemia Cells Cancer Res., December 15, 2007; 67(24): 11576 - 11584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sangha and C. Butts L-BLP25: A Peptide Vaccine Strategy in Non Small Cell Lung Cancer Clin. Cancer Res., August 1, 2007; 13(15): 4652s - 4654s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Beatty, S. E. Plevy, A. R. Sepulveda, and O. J. Finn Cutting Edge: Transgenic Expression of Human MUC1 in IL-10-/- Mice Accelerates Inflammatory Bowel Disease and Progression to Colon Cancer J. Immunol., July 15, 2007; 179(2): 735 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Leng, C. Cao, J. Ren, L. Huang, D. Chen, M. Ito, and D. Kufe Nuclear Import of the MUC1-C Oncoprotein Is Mediated by Nucleoporin Nup62 J. Biol. Chem., July 6, 2007; 282(27): 19321 - 19330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wei, H. Xu, and D. Kufe Human Mucin 1 Oncoprotein Represses Transcription of the p53 Tumor Suppressor Gene Cancer Res., February 15, 2007; 67(4): 1853 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yin, S. Kharbanda, and D. Kufe Mucin 1 Oncoprotein Blocks Hypoxia-inducible Factor 1{alpha} Activation in a Survival Response to Hypoxia J. Biol. Chem., January 5, 2007; 282(1): 257 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ren, D. Raina, W. Chen, G. Li, L. Huang, and D. Kufe MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling Mol. Cancer Res., November 1, 2006; 4(11): 873 - 883. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
