1. ¹Graduate Program in Molecular Pathology, University of California San Diego, La Jolla, CA 92037, USA
2. ²Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA

Correspondence: GS Salvesen, Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Tel: +1 858 646 3114; Fax: +1 858 713 6274; E-mail: gsalvesen@burnham.org

Received 29 August 2006; Revised 9 October 2006; Accepted 9 October 2006; Published online 3 November 2006.

Abstract

The relatively common occurrence of sequences within proteins that match the consensus substrate specificity of caspases in intracellular proteins suggests a multitude of substrates in vivo – somewhere in the order of several hundred in humans alone. Indeed, the list of proteins that are reported to be cleaved by caspases in vitro proliferates rapidly. However, only a few of these proteins have been rigorously established as biologically or pathologically relevant, bona fide substrates in vivo. Many of them probably simply represent 'innocent bystanders' or erroneous assignments. In this review we discuss concepts of caspase substrate recognition and specificity, give resources for the discovery and annotation of caspase substrates, and highlight some specific human or mouse proteins where there is strong evidence for biologic or pathologic relevance.