Interplay between Cdh1 and JNK activity during the cell cycle.
The ubiquitin ligase APC/C(Cdh1) coordinates degradation of key cell cycle regulators. We report here that a nuclear-localized portion of the stress-activated kinase JNK is degraded by the APC/C(Cdh1) during exit from mitosis and the G1 phase of the cell cycle. Expression of a non-degradable JNK induces prometaphase-like arrest and aberrant mitotic spindle dynamics. Moreover, JNK phosphorylates Cdh1 directly, during G2 and early mitosis, changing its subcellular localization and attenuating its ability to activate the APC/C during G2/M. This regulatory mechanism between JNK and Cdh1 reveals an important function for JNK during the cell cycle.
Gutierrez
Gustavo J
GJ
Signal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
Tsuji
Toshiya
T
Chen
Meifan
M
Jiang
Wei
W
Ronai
Ze'ev A
ZA
D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D010766:Phosphorylation
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D048670:MAP Kinase Kinase 4