Increased ezrin expression and activation by CDK5 coincident with acquisition of the senescent phenotype.
Passage of normal cells in culture leads to senescence, an irreversible cell cycle exit characterized by biochemical changes and a distinctive morphology. Cellular stresses, including oncogene activation, can also lead to senescence. Consistent with an anti-oncogenic role for this process, the tumor suppressor pRb plays a critical role in senescence. Reexpression of pRb in human tumor cells results in senescence-like changes including cell cycle exit and shape changes. Here we show that senescence is accompanied by increased expression and altered localization of ezrin, an actin binding protein involved in membrane-cytoskeletal signaling. pRb expression results in the stimulation of CDK5-mediated phosphorylation of ezrin with subsequent membrane association and induction of cell shape changes, linking pRb activity to cytoskeletal regulation in senescent cells.
Yang
Hai-Su
HS
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Hinds
Philip W
PW
D000595:Amino Acid Sequence / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D000099149:Ezrin
D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D016160:Retinoblastoma Protein; D000099149:Ezrin; C495905:CDK5 protein, human