Regulation of microtubule assembly and stability by the transactivator of transcription protein of Jembrana disease virus.
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.
Xuan
Chenghao
C
College of Life Sciences, Nankai University, Tianjin 300071, China.
Qiao
Wentao
W
College of Life Sciences, Nankai University, Tianjin 300071, China.
Gao
Jinmin
J
College of Life Sciences, Nankai University, Tianjin 300071, China.
Liu
Min
M
College of Life Sciences, Nankai University, Tianjin 300071, China.
Zhang
Xihui
X
College of Life Sciences, Nankai University, Tianjin 300071, China.
Cao
Youjia
Y
College of Life Sciences, Nankai University, Tianjin 300071, China.
Chen
Qimin
Q
College of Life Sciences, Nankai University, Tianjin 300071, China.
Geng
Yunqi
Y
College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: gengyq@nankai.edu.cn.
Zhou
Jun
J
College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: junzhou@nankai.edu.cn.
D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002417:Cattle; D002460:Cell Line; D002474:Cell-Free System; D006801:Humans; D017960:Lentiviruses, Bovine / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D053586:Virus Internalization
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014404:Tubulin