| Tuberous sclerosis complex 2 loss-of-function mutation regulates reactive oxygen species production through Rac1 activation. | |
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MedLine Citation:
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PMID: 18230340 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The products of the TSC1 (hamartin) and TCS2 (tuberin) tumor suppressor genes negatively regulate cell growth by inhibiting mTOR signaling. Recent research has led to the postulation that tuberin and/or hamartin are involved in tumor migration, presumably through Rho activation. Here we show that LEF-8 cells, which contain a Y1571 missense mutation in tuberin, express higher Rac1 activity than tuberin negative and positive cells. We also provide evidence of obvious lamellipodia formation in LEF-8 cells. Since the production of TSC2(Y1571H) cannot form a hetero-complex with hamartin, we further analyzed another mutant, TSC2(R611Q), which also lacks the ability to form a complex with hamartin. Introducing both forms of mutated TSC2 into COS-1 cells increased Rac1 activity as well as cell motility. We also found these two mutants interacted with Rac1. We further demonstrated that the introduction of mutated TSC2 into COS-1 cells can generate higher reactive oxygen species (ROS). These results indicate that loss-of-function mutated tuberin can activate Rac1 and thereby increase ROS production. |
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Authors:
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Tsukasa Suzuki; Swadesh K Das; Hirohumi Inoue; Machiko Kazami; Okio Hino; Toshiyuki Kobayashi; Raymond S Yeung; Ken-Ichi Kobayashi; Tadahiro Tadokoro; Yuji Yamamoto |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-01-28 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 368 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-15 Completed Date: 2008-03-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 132-7 Citation Subset: IM |
Affiliation:
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Department of Applied Biology and Chemistry, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Movement Cercopithecus aethiops Enzyme Activation Mice Mutation / genetics Protein Binding Rats Reactive Oxygen Species / metabolism* Tumor Suppressor Proteins / genetics, metabolism* rac1 GTP-Binding Protein / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 0/Tumor Suppressor Proteins; 169027-60-5/tuberous sclerosis complex 2 protein; EC 3.6.5.2/rac1 GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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