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rdf:type |
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lifeskim:mentions |
umls-concept:C0010852,
umls-concept:C0018270,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0079427,
umls-concept:C0109317,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1325410,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1704259,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1705987
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pubmed:issue |
12
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pubmed:dateCreated |
2006-3-20
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pubmed:abstractText |
NORE1A is a growth and tumor suppressor that is inactivated in a variety of cancers. NORE1A has been shown to bind to the active Ras oncogene product. However, the mechanism of NORE1A-induced growth arrest and tumor suppression remains unknown. Using anchorage-independent growth assays, we mapped the NORE1A effector domain (the minimal region of the protein responsible for its growth-suppressive effects) to the fragment containing the central and Ras association domains of NORE1A (amino acids 191-363). Expression of the NORE1A effector domain in A549 lung adenocarcinoma cells resulted in the selective inhibition of signal transduction through the ERK pathway. The full-length NORE1A (416 amino acids) and its fragments capable of growth suppression were localized to centrosomes and microtubules in normal and transformed human cells in a Ras-independent manner. A mutant that was deficient in binding to centrosomes and microtubules was also deficient in inducing cell cycle arrest. This suggests that cytoskeletal localization is required for growth-suppressive effects of NORE1A. Ras binding function was required for growth-suppressive effects of the full-length NORE1A but not for the growth-suppressive effects of the effector domain. Our studies suggest that association of NORE1A with cytoskeletal elements is essential for NORE1A-induced growth suppression and that the ERK pathway is a target for NORE1A growth-suppressive activities.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8143-52
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16421102-Blotting, Western,
pubmed-meshheading:16421102-Bronchi,
pubmed-meshheading:16421102-Cell Cycle,
pubmed-meshheading:16421102-Cell Line,
pubmed-meshheading:16421102-Cell Line, Transformed,
pubmed-meshheading:16421102-Cell Line, Tumor,
pubmed-meshheading:16421102-Cell Proliferation,
pubmed-meshheading:16421102-Centrosome,
pubmed-meshheading:16421102-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:16421102-Cytoskeleton,
pubmed-meshheading:16421102-Down-Regulation,
pubmed-meshheading:16421102-Epithelial Cells,
pubmed-meshheading:16421102-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16421102-Flow Cytometry,
pubmed-meshheading:16421102-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16421102-Genes, Tumor Suppressor,
pubmed-meshheading:16421102-Green Fluorescent Proteins,
pubmed-meshheading:16421102-Humans,
pubmed-meshheading:16421102-Immunoprecipitation,
pubmed-meshheading:16421102-MAP Kinase Signaling System,
pubmed-meshheading:16421102-Microscopy, Fluorescence,
pubmed-meshheading:16421102-Microtubules,
pubmed-meshheading:16421102-Mitogen-Activated Protein Kinases,
pubmed-meshheading:16421102-Monomeric GTP-Binding Proteins,
pubmed-meshheading:16421102-Mutation,
pubmed-meshheading:16421102-Plasmids,
pubmed-meshheading:16421102-Protein Binding,
pubmed-meshheading:16421102-Protein Structure, Tertiary,
pubmed-meshheading:16421102-Retroviridae,
pubmed-meshheading:16421102-Signal Transduction,
pubmed-meshheading:16421102-Transfection,
pubmed-meshheading:16421102-Tubulin,
pubmed-meshheading:16421102-ras Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
The growth and tumor suppressor NORE1A is a cytoskeletal protein that suppresses growth by inhibition of the ERK pathway.
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pubmed:affiliation |
Department of Pathology, University of Virginia Health Science Center, Charlottesville, Virginia 22908, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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