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PMID: 14993280 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct activities of the alpha-catenin family, alpha-catulin and alpha-catenin, on beta-catenin-mediated signaling.

Molecular and cellular biology ·Vol. 24 ·No. 6 ·2004-03-00 ·Pages 2410-22

Merdek KD, Nguyen NT, Toksoz D

Abstract

Alpha-catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of beta-catenin, a key component of the Wnt pathway, which activates T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription and is often upregulated in cancers. Recently, we identified an alpha-catenin-related protein, alpha-catulin, whose function is poorly understood, as part of a Rho GTPase signaling complex. Here, based on evidence suggesting that alpha-catulin may associate with a beta-catenin fraction, we investigated the role of alpha-catenin family members in beta-catenin-mediated signals. Expression of the full length or a 103-residue region of alpha-catenin strongly inhibits the induction of the TCF/LEF-responsive TOPFLASH reporter in HEK293T cells expressing activated beta-catenin or in cancer cells with constitutively upregulated Wnt signaling, whereas alpha-catulin expression had no effect. Interestingly, alpha-catulin expression attenuates the activation of the cyclin D1 promoter, a target of Wnt pathway signals. Alpha-catulin appears to inhibit Ras-mediated signals to the cyclin D1 promoter, rather than beta-catenin signals, and the synergy between Ras and beta-catenin required to fully activate this promoter. Data suggesting the involvement of Rho in this response are presented and discussed. These results suggest a novel function for alpha-catulin and imply that alpha-catenin and alpha-catulin have distinct activities that downregulate, respectively, beta-catenin and Ras signals converging on the cyclin D1 promoter.

MeSH Terms
Active Transport, Cell Nucleus/drug effects Amino Acid Sequence Cell Line Cyclin D1/genetics Cytoskeletal Proteins/genetics,metabolism Genes, Reporter Humans In Vitro Techniques Lithium Chloride/pharmacology Models, Biological Molecular Sequence Data Promoter Regions, Genetic Recombinant Proteins/genetics,metabolism Sequence Homology, Amino Acid Signal Transduction Trans-Activators/genetics,metabolism Transcription, Genetic Vinculin/genetics,metabolism alpha Catenin beta Catenin ras Proteins/genetics,metabolism rhoA GTP-Binding Protein/genetics,metabolism
Chemicals
CTNNA1 protein, human CTNNAL1 protein, human CTNNB1 protein, human Cytoskeletal Proteins Recombinant Proteins Trans-Activators alpha Catenin beta Catenin Vinculin Cyclin D1 ras Proteins rhoA GTP-Binding Protein Lithium Chloride
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Merdek Keith D
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. keith.merdek@tufts.edu.
Nguyen Nhan T
Toksoz Deniz
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.6.2410-2422.2004
Email
keith.merdek@tufts.edu
Published
2004-03-00
Pages
2410-22
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC355851
Subset
IM
Grants
NIDDK NIH HHS · T32 DK007542 · United States
NIDDK NIH HHS · 1 P30 DK39428 · United States
NCI NIH HHS · CA62029 · United States
NIDDK NIH HHS · T32 DK07542 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.6.2410-2422.2004 PMC Full Text View journal details
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