Senescence-associated alterations of cytoskeleton: extraordinary production of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts.
The cytoskeleton of senescent cells was systematically studied using senescent and young fibroblasts. In the cell senescence, skin fibroblasts extraordinarily produced vimentin in contrast to actin and tubulin, which were down-regulated. Among the focal adhesion proteins, paxillin and c-Src decreased also. Senescent cells developed a long and dense vimentin network, long and thin actin fibers, and numerous small focal contact sites, which contrasted with young cells with short and thick actin stress fibers and prominently large focal adhesions. Noticeably, senescent fibroblasts markedly produced p53 molecules and anchored them to vimentin-cytoskeleton in the cytoplasm. The vimentin-anchored p53 was detected with antibody PAb240 that specifically recognizes a conformation variant of p53. A GFP-tagged wild type p53 cDNA was expressed by transfection and shown also to be retained in the cytoplasm in senescent cells, suggesting that p53 is structurally modified to be recognized by PAb240 and anchored to vimentin filaments. We discuss the correlation of the marked alteration of cytoskeleton and senescent cells' diminished proliferation and migration, as well as the significance of cytoskeletal anchorage of tumor suppressor p53.
Nishio
Koji
K
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Showa-Ku, Nagoya, Aich 466-8550, Japan. knishio@med.nagoya-u.ac.jp
Inoue
Akira
A
D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D022502:Stress Fibers; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism*
D000199:Actins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D018809:Proliferating Cell Nuclear Antigen; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D014746:Vimentin
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