JIP4 is a PLK1 binding protein that regulates p38MAPK activity in G2 phase

• Published in: Cellular signalling 2015-11, Vol.27 (11), p.2296-2303
• Main Authors: Pinder, Alex, Loo, Dorothy, Harrington, Brittney, Oakes, Vanessa, Hill, Michelle M., Gabrielli, Brian
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; CDC2 Protein Kinase; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cyclin B - metabolism; Cyclin-Dependent Kinases - metabolism; G2 phase; G2 Phase - genetics; HEK293 Cells; HeLa Cells; Humans; JIP4; M Phase Cell Cycle Checkpoints - genetics; Mitosis; Mitosis - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; p38MAPK; Phosphorylation; PLK1; Polo-Like Kinase 1; Protein Binding - physiology; Protein Serine-Threonine Kinases - metabolism; Protein Structure, Tertiary; Proto-Oncogene Proteins - metabolism; RNA Interference; RNA, Small Interfering - genetics
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2015.08.009

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. •PLK1 binds to the MAPK scaffold protein JIP4 in G2 phase of the cell cycle via its Polobox domain.•PLK1 binding to self-priming mechanism•PLK1 binding is necessary for JIP4 dependent activation of p38MAPK in G2 phase.•JIP4 is not required for stress activated p38MAPK in either G2 phase or mitosis.