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p600, a unique protein required for membrane morphogenesis and cell survival
Yoshihiro Nakatani *,,
Hiroaki Konishi *,
Hisanori Kurooka * ¶,
Keiichiro Ishiguro * ||,
Jun-ichi Sawada * **,
Tsuyoshi Ikura *,
Stanley J. Korsmeyer *,
Jun Qin, and
Anna M. Herlitz *
*DanaFarber Cancer Institute, Harvard Medical School, Boston, MA 02115; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Departments of Biochemistry of Cell Biology, Baylor College of Medicine, Houston, TX 77030
Communicated by C. David Allis, The Rockefeller University, New York, NY, August 26, 2005
Received for publication July 20, 2005.
In this article, we identify and characterize p600, a unique600-kDa retinoblastoma protein- and calmodulin-binding protein.In the nucleus, p600 and retinoblastoma protein seem to actas a chromatin scaffold. In the cytoplasm, p600 and clathrinform a meshwork structure, which could contribute to cytoskeletalorganization and membrane morphogenesis. Reduced expressionof p600 with interference RNA abrogates integrin-mediated ruffledmembrane formation and, furthermore, prevents activation ofintegrin-mediated survival pathways. Consequently, knockdownof p600 sensitizes cells to apoptosis induced by cell detachment.These findings provide mechanistic insight into the regulationof membrane-proximal events in tumorigenesis.
Key Words: apoptosis cancer calmodulin retinoblastoma protein
Author contributions: Y.N. and S.J.K. designed research; Y.N.,H. Konishi, A.V., H. Kurooka, K.I., J.-i.S., T.I., J.Q., andA.M.H. performed research; and Y.N. wrote the paper.
Freely available online through the PNAS open access option.