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CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma
Joint Authors
Kobayashi, Shinichi
Yokoyama, Atsushi
Ando, Kiyohiro
Cázares-Ordoñez, Verna
Makishima, Makoto
Suenaga, Yusuke
Kamijo, Takehiko
Koshinaga, Tsugumichi
Wada, Satoshi
Nagase, Hiroki
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-09-15
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Checkpoint kinase 1 (CHK1) plays a key role in genome surveillance and integrity throughout the cell cycle.
Selective inhibitors of CHK1 (CHK1i) are undergoing clinical evaluation for various human malignancies, including neuroblastoma.
Recently, we reported that CHK1i, PF-477736, induced a p53-mediated DNA damage response.
As a result, the cancer cells were able to repair DNA damage and became less sensitive to CHK1i.
In this study, we discovered that PF-477736 increased expression of MDM2 oncogene along with CHK1i-induced replication defects in neuroblastoma NB-39-nu cells.
A mass spectrometry analysis of protein binding to MDM2 in the presence of CHK1i identified the centrosome-associated family protein 131 (CEP131), which was correlated with unfavorable prognosis of neuroblastoma patients.
We revealed that MDM2 was associated with CEP131 protein degradation, whereas overexpression of CEP131 accelerated neuroblastoma cell growth and exhibited resistance to CHK1i-induced replication defects.
Thus, these findings may provide a future therapeutic strategy against centrosome-associated oncogenes involving CEP131 as a target in neuroblastoma.
American Psychological Association (APA)
Ando, Kiyohiro& Cázares-Ordoñez, Verna& Makishima, Makoto& Yokoyama, Atsushi& Suenaga, Yusuke& Nagase, Hiroki…[et al.]. 2020. CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma. Journal of Oncology،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1188882
Modern Language Association (MLA)
Ando, Kiyohiro…[et al.]. CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma. Journal of Oncology No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1188882
American Medical Association (AMA)
Ando, Kiyohiro& Cázares-Ordoñez, Verna& Makishima, Makoto& Yokoyama, Atsushi& Suenaga, Yusuke& Nagase, Hiroki…[et al.]. CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma. Journal of Oncology. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1188882
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1188882