title: Transcriptional and post-transcriptional regulation of βIII-tubulin             protein expression in relation with cell cycle-dependent regulation of tumor cells.
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.
authors.affiliation: Department of Tumor Biology, Iwate Medical University, Yahaba-cho, Iwate, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibazaki
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Akasaka
authors.forename: Shuya
authors.initials: S
authors.lastname: Kasai
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuhira
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kanno
authors.forename: Ikue
authors.initials: I
authors.lastname: Nakayama
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayasi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.forename: Nozomu
authors.initials: N
authors.lastname: Mori
mesh_terms: D002455:Cell Division / Q000235:genetics*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics / Q000379:methods; D016195:G2 Phase / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D014404:Tubulin / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014404:Tubulin; D025801:Ubiquitin; D000099229:RE1-Silencing Transcription Factor; C498585:TUBB3 protein, human