ERK5 pathway regulates the phosphorylation of tumour suppressor hDlg during mitosis.
Human disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is thought to be a tumour suppressor that regulates the cell cycle and proliferation. However, the mechanism and pathways involved in hDlg regulation during these processes is still unclear. Here we report that hDlg is phosphorylated during mitosis, and we establish the identity of at least three residues phosphorylated in hDlg; some are previously unreported. Phosphorylation affects hDlg localisation excluding it from the contact point between the two daughter cells. Our results reveal a previously unreported pathway for hDlg phosphorylation in mitosis and show that ERK5 pathway mediates hDlg cell cycle dependent phosphorylation. This is likely to have important implications in the correct timely mitotic entry and mitosis progression.
Iñesta-Vaquera
Francisco A
FA
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología-CSIC, Campus de Cantoblanco-UAM, Madrid, Spain.
Campbell
David G
DG
Arthur
J Simon C
JS
Cuenda
Ana
A
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D000074288:Discs Large Homolog 1 Protein; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D048291:Mitogen-Activated Protein Kinase 12 / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D008938:Mitosis; D010766:Phosphorylation; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D048291:Mitogen-Activated Protein Kinase 12; D048056:Mitogen-Activated Protein Kinase 9; D048054:Mitogen-Activated Protein Kinase 7; D048055:Mitogen-Activated Protein Kinase 8