title: Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression.
abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.
authors.affiliation: Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Takahashi
authors.forename: Chisato
authors.initials: C
authors.lastname: Kikuguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Morita
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Shimodaira
authors.forename: Noriko
authors.initials: N
authors.lastname: Tokai-Nishizumi
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Miho
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis; D008941:Spindle Apparatus / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C466622:CNOT3 protein, human; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors