JIP4 is a PLK1 binding protein that regulates p38MAPK activity in G2 phase.
Cell cycle progression from G2 phase into mitosis is regulated by a complex network of mechanisms, all of which finally control the timing of Cyclin B/CDK1 activation. PLK1 regulates a network of events that contribute to regulating G2/M phase progression. Here we have used a proteomics approach to identify proteins that specifically bind to the Polobox domain of PLK1. This identified a panel of proteins that were either associated with PLK1 in G2 phase and/or mitosis, the strongest interaction being with the MAPK scaffold protein JIP4. PLK1 binding to JIP4 was found in G2 phase and mitosis, and PLK1 binding was self-primed by PLK1 phosphorylation of JIP4. PLK1 binding is required for JIP4-dependent p38MAPK activation in G2 phase during normal cell cycle progression, but not in either G2 phase or mitotic stress response. Finally, JIP4 is a target for caspase-dependent cleavage in mitotically arrested cells. The role for the PLK1-JIP4 regulated p38MAPK activation in G2 phase is unclear, but it does not affect either progression into or through mitosis.
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Alex
A
Pinder
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Dorothy
D
Loo
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Brittney
B
Harrington
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Vanessa
V
Oakes
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Michelle M
MM
Hill
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: brianG@uq.edu.au.
Brian
B
Gabrielli
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D019926:Cyclin B; D018844:Cyclin-Dependent Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; D000097869:Polo-Like Kinase 1; C111047:SPAG9 protein, human; C528899:CDK1 protein, human
G2 phase; JIP4; Mitosis; PLK1; p38MAPK