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J. Biol. Chem., Vol. 282, Issue 39, 28800-28806, September 28, 2007

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Regulation of Microtubule Assembly and Stability by the Transactivator of Transcription Protein of Jembrana Disease Virus^*

From the College of Life Sciences, Nankai University, Tianjin 300071, China

Microtubules are cytoskeletal polymers consisting of tubulin subunits that take part in diverse cell activities. Many viruses hijack cellular motor proteins to move on microtubules toward the cell interior during the entry process and toward the plasma membrane during the egress period. In addition, viruses often remodel microtubules to facilitate the generation of infectious progeny. In this study, we found that the transactivator of transcription protein of Jembrana disease virus (Jtat) bound tubulin and microtubules both in cells and in the purified system. Microtubule co-sedimentation and co-localization assays revealed a robust interaction of Jtat with microtubules. Tubulin turbidity assay further showed that Jtat promoted tubulin polymerization in vitro in a concentration-dependent manner. Moreover, Jtat promoted the partitioning of cellular tubulin toward the polymeric form, increased the level of tubulin acetylation, and significantly enhanced the cold stability of cellular microtubules. In addition, Jtat-mediated disruption of microtubule dynamics induced the release of Bim from microtubules, leading to profound apoptosis. These results not only identify Jtat as an important viral regulator of microtubule dynamics but also indicate that Jtat-induced apoptosis might contribute to Jembrana disease pathogenesis.

Received for publication, April 3, 2007 , and in revised form, July 18, 2007.

^* This work was supported by grants from the National Basic Research Program of China (2006CB910100 and 2007CB914802) and the National Natural Science Foundation of China (30600313). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S4.

¹ To whom correspondence may be addressed: College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin 300071, China. Tel. and Fax: 86-22-2350-4946; E-mail: gengyq{at}nankai.edu.cn.

² To whom correspondence may be addressed. E-mail: junzhou{at}nankai.edu.cn.

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