Tpl-2 induces apoptosis by promoting the assembly of protein complexes that contain caspase-9, the adapter protein Tvl-1, and procaspase-3

✍ Scribed by Christos Patriotis; Maria G. Russeva; Jun-Hsiang Lin; Srinivasa M. Srinivasula; Dessislava Z. Markova; Christos Tsatsanis; Antonios Makris; Emad S. Alnemri; Philip N. Tsichlis

• Book ID: 102312232
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 304 KB
• Volume: 187
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1066

✦ Synopsis

Abstract

The Tpl‐2 proto‐oncoprotein promotes cellular proliferation when overexpressed in a variety of tumor cell lines. Here, we present evidence that when overexpressed in immortalized non‐transformed cells, Tpl‐2 induces apoptosis by promoting the activation of caspase‐3 via a caspase‐9‐dependent mechanism, and that apoptosis is enhanced when Tpl‐2 is co‐expressed with the newly identified ankyrin repeat protein Tvl‐1. The activation of caspase‐3 by caspase‐9 is known to depend on the assembly of a multimolecular complex that includes Apaf‐1 and caspase‐9. Data presented here show that co‐expression of Tpl‐2 with Tvl‐1 promotes the assembly of a complex that involves several proteins that bind Apaf‐1 including Tvl‐1, itself, Tpl‐2 and phosphorylated procaspase‐9. More important, procaspase‐3, which under normal growth conditions is not associated with the complex, binds Tvl‐1 conditionally in response to Tpl‐2–generated apoptotic signals. The conditional association of procaspase‐3 with Tvl‐1 promotes the in vivo proteolytic maturation of procaspase‐3 by caspase‐9, a process casually linked to apoptosis. © 2001 Wiley‐Liss, Inc.