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Title: Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

Abstract

Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- 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:
 [1];  [2]; ; ; ; ; ;  [1];  [1];  [3]
  1. Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan)
  2. Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan)
  3. (Japan)
Publication Date:
OSTI Identifier:
22207742
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 419; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL PROLIFERATION; GENE REGULATION; GENES; INHIBITION; MESSENGER-RNA; METABOLISM; MITOSIS; MITOTIC INDEX; PROTEINS

Citation Formats

Takahashi, Akinori, Kikuguchi, Chisato, Morita, Masahiro, Shimodaira, Tetsuhiro, Tokai-Nishizumi, Noriko, Yokoyama, Kazumasa, Ohsugi, Miho, Suzuki, Toru, Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp, and Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.02.007.
Takahashi, Akinori, Kikuguchi, Chisato, Morita, Masahiro, Shimodaira, Tetsuhiro, Tokai-Nishizumi, Noriko, Yokoyama, Kazumasa, Ohsugi, Miho, Suzuki, Toru, Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp, & Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression. United States. doi:10.1016/J.BBRC.2012.02.007.
Takahashi, Akinori, Kikuguchi, Chisato, Morita, Masahiro, Shimodaira, Tetsuhiro, Tokai-Nishizumi, Noriko, Yokoyama, Kazumasa, Ohsugi, Miho, Suzuki, Toru, Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp, and Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412. Fri . "Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression". United States. doi:10.1016/J.BBRC.2012.02.007.
@article{osti_22207742,
title = {Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression},
author = {Takahashi, Akinori and Kikuguchi, Chisato and Morita, Masahiro and Shimodaira, Tetsuhiro and Tokai-Nishizumi, Noriko and Yokoyama, Kazumasa and Ohsugi, Miho and Suzuki, Toru and Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp and Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412},
abstractNote = {Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- 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.},
doi = {10.1016/J.BBRC.2012.02.007},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 419,
place = {United States},
year = {Fri Mar 09 00:00:00 EST 2012},
month = {Fri Mar 09 00:00:00 EST 2012}
}