The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation
Open accessAbstract
β-Catenin is a protein that plays a role in intercellular adhesion as well as in the regulation of gene expression. The latter role of β-catenin is associated with its oncogenic properties due to the loss of expression or inactivation of the tumor suppressor adenomatous polyposis coli (APC) or mutations in β-catenin itself. We now demonstrate that another tumor suppressor, PTEN, is also involved in the regulation of nuclear β-catenin accumulation and T cell factor (TCF) transcriptional activation in an APC-independent manner. We show that nuclear β-catenin expression is constitutively elevated in PTEN null cells and this elevated expression is reduced upon reexpression of PTEN. TCF promoter/luciferase reporter assays and gel mobility shift analysis demonstrate that PTEN also suppresses TCF transcriptional activity. Furthermore, the constitutively elevated expression of cyclin D1, a β-catenin/TCF–regulated gene, is also suppressed upon reexpression of PTEN. Mechanistically, PTEN increases the phosphorylation of β-catenin and enhances its rate of degradation. We define a pathway that involves mainly integrin-linked kinase and glycogen synthase kinase 3 in the PTEN-dependent regulation of β-catenin stability, nuclear β-catenin expression, and transcriptional activity. Our data indicate that β-catenin/TCF–mediated gene transcription is regulated by PTEN, and this may represent a key mechanism by which PTEN suppresses tumor progression.
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Cites
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Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
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Cited by
The protein kinase B/Akt signalling pathway in human malignancy
Nicholson, K. M., & Anderson, N. G. (2002) · Cellular Signalling · doi:10.1016/s0898-6568(01)00271-6 · Cited by 1,639
Protean PTEN: Form and Function
Waite, K. A., & Eng, C. (2002) · The American Journal of Human Genetics · doi:10.1086/340026 · Cited by 457
Integrin-linked kinase (ILK) and its interactors
Wu, C., & Dedhar, S. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200108077 · Cited by 447
Self-citationTumor and its microenvironment: A synergistic interplay
Catalano, V., Turdo, A., Di Franco, S., Dieli, F., Todaro, M., & Stassi, G. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.08.007 · Cited by 444
PTEN-deficient intestinal stem cells initiate intestinal polyposis
He, X. C., Yin, T., Grindley, J. C., Tian, Q., Sato, T., Tao, W. A., Dirisina, R., Porter-Westpfahl, K. S., Hembree, M., Johnson, T., et al. (2007) · Nature Genetics · doi:10.1038/ng1928 · Cited by 417
Metadata
- Authors
- Persad, S., A.Troussard, A., McPhee, T. R., Mulholland, D. J., & Dedhar, S.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-06-04
- Volume
- 153
- Issue
- 6
- Pages
- 1161-1174
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W1987162584
- Cited by
- 268
- References
- 53
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Persad, S., A.Troussard, A., McPhee, T. R., Mulholland, D. J., & Dedhar, S. (2001). Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation. The Journal of Cell Biology. https://doi.org/10.1083/jcb.153.6.1161
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