Oncotarget

Research Papers:

Pellino 1 inactivates mitotic spindle checkpoint by targeting BubR1 for ubiquitinational degradation

Jihyun Park, Hye-Young Park, Suhyeon Kim, Hyun-Soo Kim, Ji Y. Park, Heounjeong Go and Chang-Woo Lee _

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Oncotarget. 2017; 8:32055-32067. https://doi.org/10.18632/oncotarget.16762

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Abstract

Jihyun Park1,*, Hye-Young Park2,*, Suhyeon Kim3, Hyun-Soo Kim3, Ji Y. Park4, Heounjeong Go5, Chang-Woo Lee1,3

1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea

2MOGAM Institute for Biomedical Research, Yongin 16924, Republic of Korea

3Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea

4Department of Pathology, Daegu Catholic University Medical Center, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea

5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea

*These authors contributed equally to this work

Correspondence to:

Chang-Woo Lee, email: cwlee1234@skku.edu

Hye-Young Park, email: phy@mogam.re.kr

Keywords: Pellino 1, BubR1, receptor-mediated signalling, mitotic spindle checkpoint, aneuploidy

Received: January 25, 2017     Accepted: March 22, 2017     Published: March 31, 2017

ABSTRACT

Aberrant constitutive activation of receptor-mediated downstream signalling plays an active role in the deregulation of cell cycle control. The mitotic spindle checkpoint is important in preventing abnormal mitotic cell cycle with chromosome missegregation from achieving neoplastic aneuploidy. However, mechanisms coupling receptor-mediated signalling to mitotic spindle checkpoint regulation remain unclear. Pellino 1 is a receptor signal-responsive E3 ubiquitin ligase, and the application of certain receptor-mediated signalling regulates the expression and activity of Pellino 1. In the present study, Pellino 1 expression induced extensive chromosome aneuploidy and allowed abnormal mitotic cells to adapt and become aneuploid in vitro and in vivo. Pellino 1 directly interacted with BubR1, a key component of mitotic spindle checkpoint, in a mitotic cell-cycle dependent manner, and down-regulated the stability of BubR1 by ubiquitination-mediated degradation and induced mitotic dysfunction. In summary, Pellino 1 expression acts as an inhibitory signal of the homeostatic regulation of mitotic cell cycle and checkpoint, and thus contributes to the initiation and progression of neoplastic chromosome aneuploidy.


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