A Little About Destruction Box
Proteolysis by ubiquitin and 26S proteasome pathway is a fundamental mechanism for protein
turnover, cell cycle control and signal transudation.
The ubiquitin pathway is a multi-step process in which an ubiquitin molecule is activated by
an E1 enzyme, transferred to an E2 enzyme, and then covalently attached to the protein
substrate either directly or in conjunction with E3 enzyme (ubiquitin ligase). Proteins
destined to be degraded are subject to multiple rounds of ubiquitin attachment and are then
proteolyzed by the 26S proteasome. E3 enzymes are involved in protein substrate recognition and
thereby confer specificity to the ubiqitination reaction.
The anaphase promoting complex (APC), or cyclosome, is a multi-subunit E3 protein. APC is
responsible for ubiquitination of cell regulators at the metaphase - anaphase and mitosis - G1
transitions. Two degradation motifs have been identified in APC substrates: destruction box
(D - box) and KEN box. Most APC substrates have D box and some have either a KEN box or both
D and KEN boxes. In some cases two D boxes appear in the same protein.
