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Citation
Wong, H.W., Shaukat, Z., Wang, J., Saint, R., Gregory, S.L. (2014). JNK signaling is needed to tolerate chromosomal instability.  Cell Cycle 13(4): 622--631.
FlyBase ID
FBrf0224313
Publication Type
Research paper
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 G 2 phase enhances the apoptosis, while lengthening G 2 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.

PubMed ID
PubMed Central ID
PMC3988119 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Cycle
    Title
    Cell Cycle
    Publication Year
    2002
    ISBN/ISSN
    1538-4101 1551-4005
    Data From Reference