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 mesh-work structure, which could contribute to...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (42), p.15093-15098
Main Authors: Nakatani, Yoshihiro, Konishi, Hiroaki, Alex Vassilev, Hisanori Kurooka, Keiichiro Ishiguro, Jun-ichi Sawada, Tsuyoshi Ikura, Korsmeyer, Stanley J., Qin, Jun, Anna M. Herlitz
Format: Article
Language:English
Subjects:
Actins
Antibodies
Apoptosis
Apoptosis - physiology
Biological Sciences
Calmodulin - metabolism
Calmodulin-Binding Proteins - genetics
Calmodulin-Binding Proteins - metabolism
Cell Membrane - physiology
Cell Surface Extensions - metabolism
Cell Surface Extensions - ultrastructure
Cell Survival
Cell Transformation, Neoplastic
Cells
Cells, Cultured
Cellular biology
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
Cytoskeleton
Enzyme Activation
Fibroblasts - cytology
Fibroblasts - metabolism
HeLa cells
Human papillomavirus 16
Humans
Integrins - metabolism
Membranes
Microtubules
Molecular Sequence Data
Morphogenesis
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Protein Binding
Proteins
Retinoblastoma Protein - metabolism
RNA Interference
Ruffles
Tumors
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Summary: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 mesh-work 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 integrinmediated 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507458102