SignalSilence^® APC11 siRNA I #14100

Eukaryotic cell proliferation depends strictly upon the E3 ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C), whose main function is to trigger the transition of the cell cycle from metaphase to anaphase. The APC/C complex promotes the assembly of polyubiquitin chains on substrate proteins in order to target these proteins for degradation by the 26S proteasome (1,2). The vertebrate APC/C complex consists of as many as 15 subunits, including multiple scaffold proteins, two catalytic subunits (APC2, APC11), and a number of proteins responsible for substrate recognition (3). All E3 enzymes, including APC/C, utilize ubiquitin residues activated by E1 enzymes and transferred to E2 enzymes. Research studies indicate that APC/C interacts with the E2 enzymes UBE2S and UBE2C via the RING-finger domain-containing subunit APC11 (4-6). APC/C function relies on multiple cofactors, including an APC/C coactivator formed by the cell division control protein 20 homolog (CDC20) and Cdh1/FZR1. The CDC20/Cdh1 coactivator is responsible for recognition of APC/C substrates through interaction with specific D-box and KEN-box recognition elements within these substrates (7-9).
Anaphase-promoting complex subunit 11 (APC11) harbors a RING-H2 motif, which is characterized by a series of non-tandem His and Cys residues responsible for the coordination of zinc cations. At the primary amino acid level, APC11 displays sequence similarity to RING-box proteins RBX1 and RBX2, which are the RING-H2 motif-containing subunits of SCF ubiquitin ligase complexes (10). A heterodimer complex containing APC11 and the cullin-like subunit, APC2, forms the catalytic core of the APC/C and is critical for the APC/C to catalyze ubiquitin chain elongation (4,11).