RASSF1C, an Isoform of the Tumor Suppressor RASSF1A, Promotes the Accumulation of β-Catenin by Interacting with βTrCP
| Autor: | E. Estrabaud, Eric Quéméneur, Erwann Le Rouzic, Richard Benarous, Florence Margottin-Goguet, Laurent Daviet, Valérie Tanchou, Guillaume Blot, Irina Lassot |
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| Rok vydání: | 2007 |
| Předmět: |
Cell Nucleus
Gene isoform Cytoplasm endocrine system Cancer Research Small interfering RNA Tumor suppressor gene Tumor Suppressor Proteins Amino Acid Motifs RNA Plasma protein binding Biology beta-Transducin Repeat-Containing Proteins Molecular biology Serine Oncology WD40 repeat Humans Gene silencing Gene Silencing RNA Small Interfering beta Catenin HeLa Cells Protein Binding |
| Zdroj: | Cancer Research. 67:1054-1061 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-06-2530 |
| Popis: | The Ras-association domain family 1 (RASSF1) gene has seven different isoforms; isoform A is a tumor-suppressor gene (RASSF1A). The promoter of RASSF1A is inactivated in many cancers, whereas the expression of another major isoform, RASSF1C, is not affected. Here, we show that RASSF1C, but not RASSF1A, interacts with βTrCP. Binding of RASSF1C to βTrCP involves serine 18 and serine 19 of the SS18GYXS19 motif present in RASSF1C but not in RASSF1A. This motif is reminiscent of the canonical phosphorylation motif recognized by βTrCP; however, surprisingly, the association between RASSF1C and βTrCP does not occur via the βTrCP substrate binding domain, the WD40 repeats. Overexpression of RASSF1C, but not of RASSF1A, resulted in accumulation and transcriptional activation of the β-catenin oncogene, due to inhibition of its βTrCP-mediated degradation. Silencing of RASSF1A by small interfering RNA was sufficient for β-catenin to accumulate, whereas silencing of both RASSF1A and RASSF1C had no effect. Thus, RASSF1A and RASSF1C have opposite effects on β-catenin degradation. Our results suggest that RASSF1C expression in the absence of RASSF1A could play a role in tumorigenesis. [Cancer Res 2007;67(3):1054–61] |
| Databáze: | OpenAIRE |
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