p600, a unique protein required for membrane morphogenesis and cell survival.
In this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin scaffold. In the cytoplasm, p600 and clathrin form a meshwork structure, which could contribute to cytoskeletal organization and membrane morphogenesis. Reduced expression of p600 with interference RNA abrogates integrin-mediated ruffled membrane formation and, furthermore, prevents activation of integrin-mediated survival pathways. Consequently, knockdown of p600 sensitizes cells to apoptosis induced by cell detachment. These findings provide mechanistic insight into the regulation of membrane-proximal events in tumorigenesis.
Nakatani
Yoshihiro
Y
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. nakatani@mac.com
Konishi
Hiroaki
H
Vassilev
Alex
A
Kurooka
Hisanori
H
Ishiguro
Keiichiro
K
Sawada
Jun-ichi
J
Ikura
Tsuyoshi
T
Korsmeyer
Stanley J
SJ
Qin
Jun
J
Herlitz
Anna M
AM
D017209:Apoptosis / Q000502:physiology; D002147:Calmodulin / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D016023:Integrins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; C505833:UBR4 protein, human; D044767:Ubiquitin-Protein Ligases