Abstract:
:The tumor suppressor protein p53 localizes to microtubules (MT) and, in response to DNA damage, is transported to the nucleus via the MT minus-end-directed motor protein dynein. Dynein is also responsible for MT-mediated nuclear targeting of adenovirus type 2 (Ad2). Here we show that treatment with low concentrations of MT-targeting compounds (MTCs) that do not disrupt the MT network but are known to suppress MT dynamics enhanced p53 nuclear accumulation, and the activation of the p53-downstream target genes. p53 nuclear accumulation required binding of MTCs to MTs and enhanced the induction of p53-up-regulated modulator of apoptosis (PUMA) mRNA and apoptosis on challenging cells with the DNA-damaging drug adriamycin. Low concentrations of MTCs enhanced the rate of movement of fluorescent Ad2 to the nucleus and increased the nuclear targeting efficiency of Ad2. We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting.
journal_name
Proc Natl Acad Sci U S Aauthors
Giannakakou P,Nakano M,Nicolaou KC,O'Brate A,Yu J,Blagosklonny MV,Greber UF,Fojo Tdoi
10.1073/pnas.132275599keywords:
subject
Has Abstractpub_date
2002-08-06 00:00:00pages
10855-60issue
16eissn
0027-8424issn
1091-6490pii
132275599journal_volume
99pub_type
杂志文章abstract::The neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEA sulfate (DHEAS), and allopregnanolone (Allo), produced by the CNS and the adrenals, appear to exert a protective effect in hippocampal and cortical neuron ischemia- and excitotoxicity-induced injury. We hypothesized that they may also play ...
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:2015-09-29 00:00:00
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更新日期:2005-08-23 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:1987-02-01 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:2009-10-13 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: 临床试验,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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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-07-16 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:2013-07-09 00:00:00
abstract::Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified an autocrine FGF signaling induced by loss of Pten in keratinocytes. In this study, we demonstrate ...
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:2016-11-15 00:00:00
abstract::The role of cell surface immunoglobulin in helper T-cell-dependent B-cell activation was analyzed using a B-cell lymphoma, CH12, with known antigen specificity and activation properties similar to those of a resting B cell. Two sources of helper T cells were used, both selected such that they interact with H-2-encoded...
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.81.8.2466
更新日期:1984-04-01 00:00:00