학술논문

Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis.
Document Type
Academic Journal
Author
Boosen M; Institute of Genetics, University of Bonn, Römerstr. 164, D-53117 Bonn, Germany.; Vetterkind SKoplin AIllenberger SPreuss U
Source
Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0014-4827 (Print) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE
Subject
Language
English
ISSN
0014-4827
Abstract
Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm and is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis.