A novel functional screen in human cells identifies MOCA as a negative regulator of Wnt signaling.

Molecular Biology of the Cell
E Caspi, R Rosin-Arbesfeld

Abstract

Aberrant Wnt signal transduction is involved in many human diseases such as cancer and neurodegenerative disorders. The key effector protein of the canonical Wnt pathway is beta-catenin, which functions with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate gene transcription that leads to expression of Wnt target genes. In this study we provide results obtained from a novel functional screen of a human brain cDNA library used to identify 63 genes that are putative negative Wnt regulators. These genes were divided into eight functional groups that include known canonical and noncanonical Wnt pathway components and genes that had not yet been assigned to the Wnt pathway. One of the groups, the presenilin-binding proteins, contains the modifier of cell adhesion (MOCA) gene. We show that MOCA is a novel inhibitor of Wnt/beta-catenin signaling. MOCA forms a complex with beta-catenin and inhibits transcription of known Wnt target genes. Epistasis experiments indicate that MOCA acts to reduce the levels of nuclear beta-catenin, increase the levels of membrane-bound beta-catenin, and enhances cell-cell adhesion. Therefore, our data indicate that MOCA is a novel Wnt negative regulator and demonstrate that this screening appr...Continue Reading

References

Dec 10, 1993·Science·B RubinfeldP Polakis
Jun 13, 1998·Molecular Pathology : MP·R Donnellan, R Chetty
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·A TakashimaB Wolozin
Jan 20, 1999·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·S ShibamotoS Takada
Jun 15, 2000·Journal of Neurochemistry·A KashiwaH Kimura
Aug 26, 2000·Cytokine & Growth Factor Reviews·T Akiyama
Sep 7, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·I M LefterovJ S Lazo
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·L BakiN K Robakis
Sep 5, 2001·Current Opinion in Genetics & Development·J Huelsken, W Birchmeier
Dec 26, 2001·EMBO Reports·Frank J T StaalHans C Clevers
Feb 9, 2002·The Journal of Biological Chemistry·Mascha van NoortHans Clevers
May 15, 2002·The EMBO Journal·Adam Hurlstone, Hans Clevers
Jun 1, 2002·Science·Randall T MoonNorbert Perrimon
Jan 14, 2004·The Journal of Biological Chemistry·Kazuhiko NamekataHideo Kimura
Feb 13, 2004·Developmental Cell·Stephen W Wilson, Corinne Houart
Mar 6, 2004·Science·W James Nelson, Roel Nusse
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Catriona Y Logan, Roel Nusse
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qi ChenDavid Schubert
Apr 16, 2005·Nature Reviews. Neuroscience·Lorenza Ciani, Patricia C Salinas
Aug 16, 2005·Cell Calcium·Aimee D Kohn, Randall T Moon
Jun 17, 2006·Annual Review of Neuroscience·Mireille MontcouquiolMatthew W Kelley
Dec 2, 2006·Nature Reviews. Drug Discovery·Nick Barker, Hans Clevers
Dec 5, 2006·Oncogene·G V De Ferrari, R T Moon
Sep 15, 2007·Journal of Cellular Biochemistry·Nancy Gavert, Avri Ben-Ze'ev

❮ Previous
Next ❯

Citations

Feb 25, 2014·Communicative & Integrative Biology·Lei Shi
Feb 18, 2015·The International Journal of Biochemistry & Cell Biology·Xingli ZhuCaicun Zhou
Feb 5, 2015·Science Signaling·Matthew P WalkerMichael B Major
Sep 12, 2017·Nature Biotechnology·Yosef E MaruvkaGad Getz
Mar 18, 2020·Cancers·Larissa Kotelevets, Eric Chastre
Aug 20, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Changhwan JangEun-Kyoung Choi
Mar 8, 2018·Cancer Discovery·Catherine S GrassoUlrike Peters
Apr 9, 2015·Development·Sharan SwarupEsther M Verheyen
Sep 24, 2021·Oncogenesis·Tamar EvronRina Rosin-Arbesfeld

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.