Abstract:
:The Raf family includes three members, of which B-Raf is frequently mutated in melanoma and other tumors. We show that Raf-1 and A-Raf require Hsp90 for stability, whereas B-Raf does not. In contrast, mutated, activated B-Raf binds to an Hsp90-cdc37 complex, which is required for its stability and function. Exposure of melanoma cells and tumors to the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in the degradation of mutant B-Raf, inhibition of mitogen-activated protein kinase activation and cell proliferation, induction of apoptosis, and antitumor activity. These data suggest that activated mutated B-Raf proteins are incompetent for folding in the absence of Hsp90, thus suggesting that the chaperone is required for the clonal evolution of melanomas and other tumors that depend on this mutation. Hsp90 inhibition represents a therapeutic strategy for the treatment of melanoma.
journal_name
Proc Natl Acad Sci U S Aauthors
Grbovic OM,Basso AD,Sawai A,Ye Q,Friedlander P,Solit D,Rosen Ndoi
10.1073/pnas.0609973103keywords:
subject
Has Abstractpub_date
2006-01-03 00:00:00pages
57-62issue
1eissn
0027-8424issn
1091-6490pii
0609973103journal_volume
103pub_type
杂志文章abstract::Ultraviolet photosensitivity of the single-stranded forms of poly(A) and poly(dA) is compared. In contrast to poly(A), poly(dA) is rather sensitive to ultraviolet irradiation. Relatively low doses of ultraviolet light lead to characteristic changes of the ultraviolet and circular dichroism spectra of poly(dA), suggest...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.9.2683
更新日期:1973-09-01 00:00:00
abstract::A glnB gene is identified in the cyanobacterium Synechococcus sp. PCC 7942, and its gene product is found to be covalently modified as a result of imbalance in electron transfer in photosynthesis, where photosystem II is favored over photosystem I. The gene was cloned and sequenced and found to encode a polypeptide of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.11.4565
更新日期:1991-06-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2017-03-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.13.7451
更新日期:1998-06-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0903570106
更新日期:2009-06-30 00:00:00
abstract::DNA in the macronuclei of Oxytricha fallax, as in other hypotrichous ciliate protozoa, exists as small, achromosomal molecules rather than in chromosomes. We report studies on O. fallax DNA using physicochemical procedures and nucleic acid hybridization. Macronuclear DNA molecules range in size from 22 kilobase pairs ...
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
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abstract::The relative importance of local ecological and larger-scale historical processes in causing differences in species richness across the globe remains keenly debated. To gain insight into these questions, we investigated the assembly of plant diversity in the Cerrado in South America, the world's most species-rich trop...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.9.2990
更新日期:1985-05-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2000-11-07 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
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abstract::Gene regulation is a process with many steps allowing for stochastic biochemical reactions, which leads to expression noise-i.e., the cell-to-cell stochastic fluctuation in protein abundance. Such expression noise can give rise to drastically diverse phenotypes, even within isogenic cell populations. Although numerous...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2010-06-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-02-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-08-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::By using harmonic radar, we report the complete flight paths of displaced bees. Test bees forage at a feeder or are recruited by a waggle dance indicating the feeder. The flights are recorded after the bees are captured when leaving the hive or the feeder and are released at an unexpected release site. A sequence of b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2018-07-17 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::It has been hypothesized that the overall size of-or efficiency of carbon export from-the biosphere decreased at the end of the Great Oxidation Event (GOE) (ca. 2,400 to 2,050 Ma). However, the timing, tempo, and trigger for this decrease remain poorly constrained. Here we test this hypothesis by studying the isotope ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::To explore the lethal, ataxic phenotype of complex I deficiency in Ndufs4 knockout (KO) mice, we inactivated Ndufs4 selectively in neurons and glia (NesKO mice). NesKO mice manifested the same symptoms as KO mice including retarded growth, loss of motor ability, breathing abnormalities, and death by approximately 7 wk...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2010-06-15 00:00:00