Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-411
Giannakakou, P; Nakano, M Y; Nicolaou, K C; O'Brate, A; Yu, J; Blagosklonny, M V; Greber, U F; Fojo, T (2002). Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 99(16):10855-10860.
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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.
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|Item Type:||Journal Article, refereed|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|Dewey Decimal Classification:||570 Life sciences; biology|
|Date:||6 August 2002|
|Deposited On:||11 Feb 2008 12:15|
|Last Modified:||27 Nov 2013 23:39|
|Publisher:||National Academy of Sciences|
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