Association of an 80 kDa protein with C-CAM1 cytoplasmic domain correlates with C-CAM1-mediated growth inhibition

Luo, Weiping; Earley, Karen; Tantingco, Vicky; Hixson, Douglas C.; Liang, Tzyy-Chyau; Lin, Sue Hwa

doi:10.1038/sj.onc.1201619

Cited by 16 publications

(10 citation statements)

References 12 publications

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“…When the extracellular domains of CEACAM1-4L interact with each other across cell-cell junctions they transmit signals that include inhibition of cell proliferation (11,(52)(53)(54)(55). Signals of this sort have often been connected to the extensively studied β-catenin pathway that includes interactions with the wnt pathway (56) and the E-cadherin-mediated cell-cell adhesion pathway (57,58).…”

Section: Resultsmentioning

confidence: 99%

Direct Interaction of Tumor Suppressor CEACAM1 with Beta Catenin: Identification of Key Residues in the Long Cytoplasmic Domain

Liu

Li²,

Chen³

et al. 2008

Exp Biol Med (Maywood)

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CEACAM1-4L (carcinoembryonic antigen cell adhesion molecule 1, with 4 extracellular Ig-like domains and a long, 71 amino acid cytoplasmic domain) is expressed in epithelial cells and activated T-cells, but is down-regulated in most epithelial cell cancers and T-cell leukemias. A highly conserved sequence within the cytoplasmic domain has ca 50% sequence homology with Tcf-3 and −4, transcription factors that bind β-catenin, and to a lesser extent (32% homology), with E-cadherin that also binds β-catenin. We show by quantitative yeast two-hybrid, BIAcore, GST-pull down, and confocal analyses that this domain directly interacts with β-catenin, and that H-469 and K-470 are key residues that interact with the armadillo repeats of β-catenin. Jurkat cells transfected with CEACAM1-4L have 2-fold less activity in the TOPFLASH reporter assay, and in MCF7 breast cancer cells that fail to express CEACAM1, transfection with CEACAM1 and growth in Ca 2+ media causes redistribution of β-catenin from the cytoplasm to the cell membrane, demonstrating a functional role for the long cytoplasmic domain of CEACAM1 in regulation of β-catenin activity.

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Section: Resultsmentioning

confidence: 99%

Direct Interaction of Tumor Suppressor CEACAM1 with Beta Catenin: Identification of Key Residues in the Long Cytoplasmic Domain

Liu

Li²,

Chen³

et al. 2008

Exp Biol Med (Maywood)

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“…Ser503 may be crucial for the binding of this protein since a deletion mutant truncating the protein at Lys499, thereby eliminating Ser503, no longer had the capability of binding the CAP-80 protein. Although its identity is still unknown, CAP-80 appears important in the CEACAM1-L Ser503-dependent growth suppressive eects (Luo et al, 1998). In addition, tight association of CEACAM1-L with the actin cytoskeleton is mediated by the same 35 distal amino acids (Sadekova et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The CEACAM1-L Ser503 residue is crucial for inhibition of colon cancer cell tumorigenicity

et al. 2001

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“…A calmodulin binding site overlaps with the C-terminal end of CEACAM1-L region (Edlund et al, 1996). Truncation of the last 39 amino acids of the rat CEACAM1 homologue abrogates the binding of an unknown 80 kDa protein (Luo et al, 1998). Its binding appears important for tumor cell growth inhibition.…”

Section: Discussionmentioning

confidence: 99%

cis-Determinants in the cytoplasmic domain of CEACAM1 responsible for its tumor inhibitory function

Izzi¹,

Turbide²,

Houde³

et al. 1999

Oncogene

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CEACAM1, also known as C-CAM, BGP and CD66a, is a member of the carcinoembryonic antigen (CEA) family which is itself part of the immunoglobulin supergene family. CEACAM1 is involved in intercellular adhesion, signal transduction and tumor cell growth regulation. CEACAM1 is down-regulated in colon and prostate carcinomas, as well as in endometrial, bladder and hepatic tumors, and 30% of breast cancers. We have shown in a mouse colon tumor model that CEACAM1 with a long cytoplasmic domain inhibited the development of tumors whereas a splice variant lacking the cytoplasmic domain did not. In this study, we de®ne the subregions of the long cytoplasmic domain participating in the tumor inhibition phenotype of CEACAM1. We show that a single point mutation of Tyr488, conforming to an Immuno-receptor Tyrosine Inhibition Motif (ITIM), was sucient to reverse the in vivo tumor cell growth inhibition. Substitution or deletion of residues in the C-terminal region of the CEACAM1 cytoplasmic domain also led to reversal of tumor cell growth inhibition. This result is in agreement with our previous studies demonstrating the C-terminal region of the cytoplasmic domain in¯uences the levels of CEACAM1 Tyr phosphorylation and its association with the protein Tyr phosphatases SHP-1 and SHP-2. Furthermore, removal of the N-terminal domain of CEACAM1, essential for intercellular adhesion, did not impair the tumor inhibitory eect. These results suggest that Tyr phosphorylation or dephosphorylation of the CEACAM1 cytoplasmic domain represents a crucial step in the control of epithelial cell proliferation.

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Association of an 80 kDa protein with C-CAM1 cytoplasmic domain correlates with C-CAM1-mediated growth inhibition

Cited by 16 publications

References 12 publications

Direct Interaction of Tumor Suppressor CEACAM1 with Beta Catenin: Identification of Key Residues in the Long Cytoplasmic Domain

Direct Interaction of Tumor Suppressor CEACAM1 with Beta Catenin: Identification of Key Residues in the Long Cytoplasmic Domain

The CEACAM1-L Ser503 residue is crucial for inhibition of colon cancer cell tumorigenicity

cis-Determinants in the cytoplasmic domain of CEACAM1 responsible for its tumor inhibitory function

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