Simian virus 40 large T antigen targets the microtubule-stabilizing protein TACC2.
The large T antigens of polyomaviruses target cellular proteins that control fundamental processes, including p53 and the RB family of tumor suppressors. Mechanisms that underlie T-antigen-induced cell transformation need to be fully addressed, because as-yet unidentified target proteins might be involved in the process. In addition, recently identified polyomaviruses are associated with particular human diseases such as aggressive skin cancers. Here, we report that simian virus 40 (SV40) large T antigen interacts with the transforming acidic coiled-coil-containing protein TACC2, which is involved in stabilizing microtubules in mitosis. T antigen directly binds TACC2 and induces microtubule dysfunction, leading to disorganized mitotic spindles, slow progression of mitosis and chromosome missegregation. These mitotic defects are caused by N-terminal-deleted T antigen, which minimally interacts with TACC2, whereas T-antigen-induced microtubule destabilization is suppressed by overexpressing TACC2. Thus, TACC2 might be a key target of T antigen to disrupt microtubule regulation and chromosomal inheritance in the initiation of cell transformation.
Tei
Shuchin
S
Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo, Kumamoto, Japan.
Saitoh
Noriko
N
Funahara
Tetsushi
T
Iida
Shin-ichi
S
Nakatsu
Yuko
Y
Kinoshita
Kayo
K
Kinoshita
Yoshikazu
Y
Saya
Hideyuki
H
Nakao
Mitsuyoshi
M
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D000957:Antigens, Viral, Tumor; D002352:Carrier Proteins; C410333:TACC2 protein, human; D025521:Tumor Suppressor Proteins