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https://hdl.handle.net/2440/86658
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Type: | Journal article |
Title: | JNK signaling is needed to tolerate chromosomal instability |
Author: | Wong, H. Shaukat, Z. Wang, J. Saint, R. Gregory, S. |
Citation: | Cell Cycle, 2014; 13(4):622-631 |
Publisher: | Landes Bioscience |
Issue Date: | 2014 |
ISSN: | 1538-4101 1551-4005 |
Statement of Responsibility: | Heidi W-S Wong, Zeeshan Shaukat, Jianbin Wang, Robert Saint, and Stephen L Gregory |
Abstract: | Chromosomal instability (CIN), as a common feature of tumors, represents a potential therapeutic target if ways can be found to specifically cause apoptosis in unstably dividing cells. We have previously shown that if signaling through the JNK pathway is reduced, apoptosis is triggered in models of chromosomal instability induced by loss of the spindle checkpoint. Here we identify components upstream and downstream of JNK that are able to mediate this effect, and test the involvement of p53 and DNA damage in causing apoptosis when JNK signaling is reduced in CIN cells. We show that cell cycle progression timing has a strong effect on the apoptosis seen when JNK signaling is reduced in genetically unstable cells: a shortened G₂ phase enhances the apoptosis, while lengthening G₂ rescues the JNK-deficient CIN cell death phenotype. Our findings suggest that chromosomal instability represents a significant stress to dividing cells, and that without JNK signaling, cells undergo apoptosis because they lack a timely and effective response to DNA damage. |
Keywords: | Chromosomal instability; JNK; Drosophila; apoptosis; Mad2 |
Description: | Published Online 12 Dec 2013 |
Rights: | © 2014 Landes Bioscience |
DOI: | 10.4161/cc.27484 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/525447 http://purl.org/au-research/grants/nhmrc/1027878 |
Published version: | http://dx.doi.org/10.4161/cc.27484 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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