STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1

The novel oncogene STYK1/NOK plays critical roles in cancer development. However, its regulation during cell division is less defined. In this paper, we show that over-expression of STYK1/NOK caused mitotic arrest and cytokinesis defects. The protein level of STYK/NOK fluctuated during the cell cycl...

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Main Authors: Su-Lin Zeng, Suraj S. Patel, Mo-Qi Lv, Daphne Zhu, Wen H. Shen, Li Liu
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022033461
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author Su-Lin Zeng
Suraj S. Patel
Mo-Qi Lv
Daphne Zhu
Wen H. Shen
Li Liu
author_facet Su-Lin Zeng
Suraj S. Patel
Mo-Qi Lv
Daphne Zhu
Wen H. Shen
Li Liu
author_sort Su-Lin Zeng
collection DOAJ
description The novel oncogene STYK1/NOK plays critical roles in cancer development. However, its regulation during cell division is less defined. In this paper, we show that over-expression of STYK1/NOK caused mitotic arrest and cytokinesis defects. The protein level of STYK/NOK fluctuated during the cell cycle, with a peak at mitosis and a quick reduction upon mitotic exit. The cell cycle-related expression pattern of STYK1/NOK resembled the one of aurora kinases and polo-like kinase 1. Depletion of APC3 led to accumulation of STYK1/NOK and to the G2/M arrest. Co-immunoprecipitation experiment demonstrated the direct interaction of STYK1/NOK with CDH1. Overexpression of CDH1 shortened the half-life of STYK1/NOK. The kinase domain, but not the five D boxes, of STYK1/NOK was responsible for the interaction with CDH1. Altogether, our data demonstrated for the first time that STYK1/NOK could affect cell division, probably by directly targeting key components of APC/C such as CDH1 at late mitosis. Current study may provide a vital mechanistic clue for understanding the roles of STYK1/NOK in mitosis and cytokinesis during STYK1NOK mediated genomic instability and oncogenesis.
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spelling doaj.art-62fda44f77e542caac98bb5f308c5f962023-01-05T08:38:14ZengElsevierHeliyon2405-84402022-12-01812e12058STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1Su-Lin Zeng0Suraj S. Patel1Mo-Qi Lv2Daphne Zhu3Wen H. Shen4Li Liu5Department of Pathogen Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; Department of Radiation Oncology, Weill Cornell Medicine, New York, New York 10065, USADepartment of Radiation Oncology, Weill Cornell Medicine, New York, New York 10065, USADepartment of Radiation Oncology, Weill Cornell Medicine, New York, New York 10065, USADepartment of Radiation Oncology, Weill Cornell Medicine, New York, New York 10065, USADepartment of Radiation Oncology, Weill Cornell Medicine, New York, New York 10065, USA; Corresponding author.Department of Pathogen Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; Corresponding author.The novel oncogene STYK1/NOK plays critical roles in cancer development. However, its regulation during cell division is less defined. In this paper, we show that over-expression of STYK1/NOK caused mitotic arrest and cytokinesis defects. The protein level of STYK/NOK fluctuated during the cell cycle, with a peak at mitosis and a quick reduction upon mitotic exit. The cell cycle-related expression pattern of STYK1/NOK resembled the one of aurora kinases and polo-like kinase 1. Depletion of APC3 led to accumulation of STYK1/NOK and to the G2/M arrest. Co-immunoprecipitation experiment demonstrated the direct interaction of STYK1/NOK with CDH1. Overexpression of CDH1 shortened the half-life of STYK1/NOK. The kinase domain, but not the five D boxes, of STYK1/NOK was responsible for the interaction with CDH1. Altogether, our data demonstrated for the first time that STYK1/NOK could affect cell division, probably by directly targeting key components of APC/C such as CDH1 at late mitosis. Current study may provide a vital mechanistic clue for understanding the roles of STYK1/NOK in mitosis and cytokinesis during STYK1NOK mediated genomic instability and oncogenesis.http://www.sciencedirect.com/science/article/pii/S2405844022033461Cell cycleSTYK1/NOKAPC/CProtein-protein interactionCDH1
spellingShingle Su-Lin Zeng
Suraj S. Patel
Mo-Qi Lv
Daphne Zhu
Wen H. Shen
Li Liu
STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
Heliyon
Cell cycle
STYK1/NOK
APC/C
Protein-protein interaction
CDH1
title STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
title_full STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
title_fullStr STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
title_full_unstemmed STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
title_short STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1
title_sort styk1 nok affects cell cycle late mitosis and directly interacts with anaphase promoting complex activator cdh1
topic Cell cycle
STYK1/NOK
APC/C
Protein-protein interaction
CDH1
url http://www.sciencedirect.com/science/article/pii/S2405844022033461
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