Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells

Shibazaki,Masahiko; Maesawa,Chihaya; Akasaka,Kiyomi; Kasai,Shuya; Yasuhira,Shinji; Kanno,Kiminori; Nakayama,Ikue; Sugiyama,Toru; Wakabayasi,Go; Masuda,Tomoyuki; Mori,Nozomu

doi:10.3892/ijo.2011.1291

March 2012 Volume 40 Issue 3

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March 2012 Volume 40 Issue 3

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Article

Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells

Authors:
- Masahiko Shibazaki
- Chihaya Maesawa
- Kiyomi Akasaka
- Shuya Kasai
- Shinji Yasuhira
- Kiminori Kanno
- Ikue Nakayama
- Toru Sugiyama
- Go Wakabayasi
- Tomoyuki Masuda
- Nozomu Mori
View Affiliations / Copyright

Affiliations: Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan
Pages: 695-702
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Published online on: December 8, 2011

https://doi.org/10.3892/ijo.2011.1291
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Abstract

The expression of βIII-tubulin (TUBB3) is generally restricted to neurons, but its mRNA is often expressed at low levels in non-neuronal cells. Interestingly, however, a number of non-neural tumors occasionally express high levels of TUBB3 protein, leading to a significant resistance to taxane derivatives. However, the molecular mechanisms controlling TUBB3 expression and its turnover during normal cell growth are largely unknown. Here, we present evidence that TUBB3 expression occurs in a cell cycle-dependent manner, and that its protein levels are controlled by the ubiquitin-proteasome system. Both mRNA and protein of TUBB3 accumulated around the G2/M stage of the cell cycle, and reduction of TUBB3 expression by siRNA resulted in partial inhibition of cell growth. Furthermore, the cell cycle-dependent expression of TUBB3 was mediated by the RE-1-silencing transcription factor REST through its binding to the RE-1 element that is present in the first intron of the TUBB3 gene. These results demonstrate a novel role of TUBB3 in cell cycle progression in non-neuronal cells, and further suggest that dysregulation of the REST-TUBB3 system could be a primary cause of the TUBB3 overexpression.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells

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