DOI: 10.1083/jcb.153.6.1161. Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1

Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation

10.1083/jcb.153.6.1161

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

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.

Bibliography

Persad, S., A.Troussard, A., McPhee, T. R., Mulholland, D. J., & Dedhar, S. (2001). Tumor Suppressor Pten Inhibits Nuclear Accumulation of Î²-Catenin and T Cell/Lymphoid Enhancer Factor 1âMediated Transcriptional Activation. The Journal of Cell Biology, 153(6), 1161â1174.

Authors 5

Sujata Persad (first)
Armelle A.Troussard (additional)
Timothy R. McPhee (additional)
David J. Mulholland (additional)
Shoukat Dedhar (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:46 p.m.)
Deposited	1 year, 7 months ago (Jan. 4, 2024, 12:14 p.m.)
Indexed	2 months ago (July 1, 2025, 9:48 a.m.)
Issued	24 years, 2 months ago (June 4, 2001)
Published	24 years, 2 months ago (June 4, 2001)
Published Online	24 years, 2 months ago (June 4, 2001)
Published Print	24 years, 2 months ago (June 11, 2001)

Funders 0

None

BibTeX

@article{Persad_2001, title={Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation}, volume={153}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.153.6.1161}, DOI={10.1083/jcb.153.6.1161}, number={6}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Persad, Sujata and A.Troussard, Armelle and McPhee, Timothy R. and Mulholland, David J. and Dedhar, Shoukat}, year={2001}, month=jun, pages={1161–1174} }

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  "abstract": "<jats:p>\u03b2-Catenin is a protein that plays a role in intercellular adhesion as well as in the regulation of gene expression. The latter role of \u03b2-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 \u03b2-catenin itself. We now demonstrate that another tumor suppressor, PTEN, is also involved in the regulation of nuclear \u03b2-catenin accumulation and T cell factor (TCF) transcriptional activation in an APC-independent manner. We show that nuclear \u03b2-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 \u03b2-catenin/TCF\u2013regulated gene, is also suppressed upon reexpression of PTEN. Mechanistically, PTEN increases the phosphorylation of \u03b2-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 \u03b2-catenin stability, nuclear \u03b2-catenin expression, and transcriptional activity. Our data indicate that \u03b2-catenin/TCF\u2013mediated gene transcription is regulated by PTEN, and this may represent a key mechanism by which PTEN suppresses tumor progression.</jats:p>",
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