The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway

• Michael Shtutman

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Jacob Zhurinsky

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Inbal Simcha

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Chris Albanese

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Mark D’Amico

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Richard Pestell

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

• Avri Ben-Ze’ev

  Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

抄録

β-Catenin plays a dual role in the cell: one in linking the cytoplasmic side of cadherin-mediated cell–cell contacts to the actin cytoskeleton and an additional role in signaling that involves transactivation in complex with transcription factors of the lymphoid enhancing factor (LEF-1) family. Elevated β-catenin levels in colorectal cancer caused by mutations in β-catenin or by the adenomatous polyposis coli molecule, which regulates β-catenin degradation, result in the binding of β-catenin to LEF-1 and increased transcriptional activation of mostly unknown target genes. Here, we show that the cyclin D1 gene is a direct target for transactivation by the β-catenin/LEF-1 pathway through a LEF-1 binding site in the cyclin D1 promoter. Inhibitors of β-catenin activation, wild-type adenomatous polyposis coli, axin, and the cytoplasmic tail of cadherin suppressed cyclin D1 promoter activity in colon cancer cells. Cyclin D1 protein levels were induced by β-catenin overexpression and reduced in cells overexpressing the cadherin cytoplasmic domain. Increased β-catenin levels may thus promote neoplastic conversion by triggering cyclin D1 gene expression and, consequently, uncontrolled progression into the cell cycle.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 96 (10), 5522-5527, 1999-05-11

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1362262945842262912
• NII論文ID: 80011176955
• DOI: 10.1073/pnas.96.10.5522
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.96.10.5522
• データソース種別:
  • Crossref
  • CiNii Articles