| Novel roles of hakai in cell proliferation and oncogenesis. | |
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MedLine Citation:
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PMID: 19535458 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During tumor development, cells acquire multiple phenotypic changes upon misregulation of oncoproteins and tumor suppressor proteins. Hakai was originally identified as an E3 ubiquitin-ligase for the E-cadherin complex that regulates cell-cell contacts. Here, we present evidence that Hakai plays a crucial role in various cellular processes and tumorigenesis. Overexpression of Hakai affects not only cell-cell contacts but also proliferation in both epithelial and fibroblast cells. Furthermore, the knockdown of Hakai significantly suppresses proliferation of transformed epithelial cells. Expression of Hakai is correlated to the proliferation rate in human tissues and is highly up-regulated in human colon and gastric adenocarcinomas. Moreover, we identify PTB-associated splicing factor (PSF), an RNA-binding protein, as a novel Hakai-interacting protein. By using cDNA arrays, we have determined various specific PSF-associated mRNAs encoding proteins that are involved in several cancer-related processes. Hakai affects the ability of PSF to bind these mRNAs, and expression of PSF short hairpin RNA or a dominant-negative PSF mutant significantly suppresses proliferation of Hakai-overexpressing cells. Collectively, these results suggest that Hakai is an important regulator of cell proliferation and that Hakai may be an oncoprotein and a potential molecular target for cancer treatment. |
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Authors:
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Angélica Figueroa; Hirokazu Kotani; Yoshinobu Toda; Krystyna Mazan-Mamczarz; Eva-Christina Mueller; Albrecht Otto; Lena Disch; Mark Norman; Rasika Mohan Ramdasi; Mohammed Keshtgar; Myriam Gorospe; Yasuyuki Fujita |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-17 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 20 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-03 Completed Date: 2010-02-17 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 3533-42 Citation Subset: IM |
Affiliation:
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MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Department of Cell and Developmental Biology, University College London, London WC1E6BT, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cadherins / genetics, metabolism Cell Adhesion Cell Line Cell Line, Tumor Cell Proliferation* Endometrium / metabolism* Female Flow Cytometry Fluorescent Antibody Technique Humans Immunohistochemistry Lymph Nodes / metabolism* Mice Mutation NIH 3T3 Cells Neoplasms / genetics, metabolism, pathology Oligonucleotide Array Sequence Analysis Protein Binding RNA Interference RNA, Messenger / genetics, metabolism RNA-Binding Proteins / genetics, metabolism Ubiquitin-Protein Ligases / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Cadherins; 0/PTB-associated splicing factor; 0/RNA, Messenger; 0/RNA-Binding Proteins; EC 6.3.2.19/CBLL1 protein, human; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
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