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Inhibition of apoptosis by the actin-regulatory protein gelsolin
Title: | Inhibition of apoptosis by the actin-regulatory protein gelsolin |
Authors: | Ohtsu, Makoto Browse this author | Sakai, Norio Browse this author | Fujita, Hisakazu Browse this author | Kashiwagi, Motoi Browse this author | Gasa, Shinsei Browse this author | Shimizu, Shigeomi Browse this author | Eguchi, Yutaka Browse this author | Tsujimoto, Yoshihide Browse this author | Sakiyama, Yukio Browse this author | Kobayashi, Kunihiko Browse this author | Kuzumaki, Noboru11 Browse this author |
Authors(alt): | 葛巻, 暹11 |
Keywords: | apoptosis | CPP32 | Fas | gelsolin | Jurkat cells |
Issue Date: | Aug-1997 |
Publisher: | Nature Publishing Group |
Journal Title: | The EMBO Journal |
Volume: | 16 |
Issue: | 15 |
Start Page: | 4650 |
End Page: | 4656 |
Abstract: | Gelsolin is an actin-regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility invivo through modulation of the actin network.
In addition to its actin-regulatory function, gelsolin has also been proposed to affect cell growth. Our present experiments have tested the possible involvement of gelsolin in the regulation of apoptosis, which is significantly affected by growth. When overexpressed in Jurkat cells, gelsolin strongly inhibited apoptosis induced by anti-Fas antibody, C2-ceramide or dexamethasone, without changing the F-actin morphology or the levels of Fas or Bcl-2 family proteins. Upon the induction of apoptosis, an increase in CPP32(-like) protease activity was observed in the control vector transfectants, while it was strongly suppressed in the gelsolin transfectants.
Pro-CPP32 protein, an inactive form of CPP32 protease, remained uncleaved by anti-Fas treatment in the gelsolin transfectants, indicating that gelsolin blocks upstream of this protease. The tetrapeptide inhibitor of CPP32(-like) proteases strongly inhibited Fas-mediated apoptosis, but only partially suppressed both C2-ceramide- and dexamethasone-induced apoptosis. These data suggest that the critical target responsible for the execution of apoptosis may exist upstream of CPP32(-like) proteases in Jurkat cells and that gelsolin acts on this target to inhibit the apoptotic cell death program. |
Type: | article (author version) |
URI: | http://embojournal.npgjournals.com/ | http://hdl.handle.net/2115/720 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 葛巻 暹
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