Motifs targeted by APC/C

APC/C structure indicating where the linear motifs from substrates bind.

Motifs Targeted by APC/C

The Anaphase-Promoting Complex or Cyclosome (APC/C) is a crucial Eukaryotic cell cycle control enzyme that regulates the transition from metaphase to anaphase by targeting specific protein motifs for ubiquitination and subsequent degradation. This process is vital for cell division, ensuring accurate chromosome segregation and the proper progression of the cell cycle. The APC/C is regulated by its coactivators, Cdc20 and Cdh1, which recognize specific degradation motifs within substrate proteins. The most well-known motifs targeted by APC/C include the Destruction box (D-box), the KEN box, and the ABBA motif.

Destruction Box (D-box)

The Destruction box (D-box) is a sequence motif recognized by the APC/C coactivator Cdc20. Proteins containing a D-box are targeted for degradation during the metaphase-to-anaphase transition. The consensus sequence for the D-box is RxxLxxxxN/D, where "x" can be any amino acid. This motif is present in several key cell cycle proteins, including securin and cyclin B, whose degradation is essential for the progression of the cell cycle.

KEN Box

The KEN box is another motif that APC/C recognizes, with the consensus sequence KEN. This motif is primarily recognized by the APC/C coactivator Cdh1, which is active in late mitosis and G1 phase. Proteins with KEN boxes, such as securin and certain cyclins, are marked for degradation, leading to the exit from mitosis and the maintenance of G1 phase.

ABBA Motif

The ABBA motif, identified more recently, is also targeted by APC/C. This motif interacts with both Cdc20 and Cdh1 and has a consensus sequence of [ILVM]xFx[ILVM]x[DE], where [ILVM] represents a hydrophobic amino acid. The ABBA motif plays a role in the recognition and degradation of substrates during both the metaphase-anaphase transition and the exit from mitosis.

Regulation and Function

The APC/C's activity is tightly regulated throughout the cell cycle to ensure timely degradation of its substrates. This regulation is achieved through the binding of its coactivators, Cdc20 and Cdh1, which are themselves regulated by phosphorylation and other post-translational modifications. The precise timing of APC/C activity is crucial for maintaining genomic stability and preventing aneuploidy, a condition associated with cancer.

The targeted degradation of proteins by the APC/C is essential for several key processes in cell division, including the separation of sister chromatids, the exit from mitosis, and the establishment of the G1 phase. By controlling the stability of proteins involved in these processes, the APC/C ensures the orderly progression of the cell cycle and the faithful transmission of genetic information to daughter cells.