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

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

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)695-702
    Number of pages8
    JournalInternational journal of oncology
    Volume40
    Issue number3
    DOIs
    Publication statusPublished - 2012 Mar

    Keywords

    • Cell cycle
    • Epigenetics
    • RE-1
    • REST
    • βIII-tubulin

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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