Title

Cytoskeletal Disruption Induces T Cell Apoptosis by a Caspase-3 Mediated Mechanism

Document Type

Article

Publication Date

11-12-1999

Journal

Life Sciences

Volume

65

Issue

25

First Page

2697

Last Page

2707

URL with Digital Object Identifier

10.1016/S0024-3205(99)00538-X

Abstract

T cell apoptosis can be triggered by different mechanisms that lead to distinctive features such as cell shrinkage, membrane blebbing, phosphatidylserine externalization, and internucleosomal DNA fragmentation. Prevailing models for the induction of apoptosis place the cytoskeleton as a distal target of the death effector molecules ('executioners'). However, the cytoskeleton can also play a role in the induction of apoptosis as suggested by the finding that cytoskeletal disruption can induce apoptosis. The mechanism by which this occurs is unknown. Here, we report that T cell apoptosis by cytoskeletal disruption involves a protein synthesis-independent mechanism leading to up-regulation of caspase-3 protease activity and increased accessibility of active caspase-3 to its substrate. Thus, cytoskeleton integrity may regulate the subcellular compartmentalization of death effector molecules.