Cyclin destruction box

Peptide motifs. Proteins with certain homologous sequences are rapidly degraded. For example, proteins that have extended sequences containing proline, glutamate, serine, and threonine have half-lives of less than 2 hours. (PEST sequences are named for the one-letter abbreviations for these amino acids. See Table 5.1.) The cyclin destruction box is a set of homologous nine-residue sequences near the N-terminus of cyclins that ensures rapid ubiquination. 

The cyclosome (or APC) is a high molecular weight complex that degrades proteins containing a specific recognition sequence, the destruction box (see chapter 13.2.4). Substrates are cell cycle regulators as e.g. cyclins, kinase inhibitors and spindle-associated proteins. Importantly, some forms of the cyclosome require phosphorylation in order to be active (fig. 2.15B). It is still unclear which of the many subunits carries the E3 enzyme activity. 

The APC possesses a ubiquitin-ligase activity with specificity for substrate proteins that contain a particular sequence, the destruction box (see 13.2.4). During and after mitosis, APC-mediated specific proteolysis is observed of the mitotic cyclins B and A and of a number of other regulatory proteins. All these proteins contain one or two copies of the destruction box. 

Most substrates for APC-mediated ubiquitinylation carry a particular sequence, the destruction box. For B-type cyclins, the consensus sequence of the destruction box is R-ALGVN/D/EI-N. Deletion of the destruction box in cyclin B causes its stabilization. 

It has been shown that cyclin B has a short amino acid sequence near its /V-terminus that targets the protein for destruction between metaphase and anaphase (destruction of cyclin B is mediated by ubiqui-tin-mediated proteolysis). Removal of this sequence (known as a destruction box) renders the cyclin indestructible, and shows that cyclin destruction is necessary for chromosome decondensation, nuclear envelope reformation and cytokinesis, but not for sister chromatid segregation. 

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