APC/C Signaling Pathway
The anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin
ligase involved in cell cycle, metabolism, DNA damage repair, autophagy, apoptosis,
aging, tumors and a variety of biological processes. As an important
post-translational modification, ubiquitination regulates protein degradation by the
ubiquitin-proteasome system (UPS). APC/C has a large molecular weight and consists
of multiple subunits. It plays an important role in cell cycle regulation and can
precisely regulate cell cycle transition by mediating ubiquitination of cell
cycle-associated proteins and is co-activated by CDC20 or regulation of CDH1.
Understanding the structure and function of APC/C is critical for studying biological
events such as cell cycle and post-translational modification of proteins. In recent
years, great progress has been made in the analysis of the structure and composition
of APC/C molecules, and its role in tumors and potential therapeutic applications
have also received attention.
APC/C family
APC/C is a giant multi-subunit protein complex having a molecular weight of about
1.2 MD. In mammals, its core is composed of at least 19 subunits. In addition to the
core, APC/C binds to the co-activator molecule CDC20 or CDH1, which is responsible
for the attachment of substrates and regulation of APC/C activity. According to a
recent analysis of the molecular structure of APC/C by Barford's research group,
APC/C can be divided into three sub-complexes, which are the scarffolding, the
catalytic and substrate recognition core and the TPR arm containing a peptide repeat
domain. The scaffold subcomplex platform includes APC1, APC4, and APC5, and the
catalytic and substrate recognition cores include APC2, APC10, APC11, and
CDC20/CDH1. The TPR arm includes APC3, APC6, APC7, APC8, APC12, APC13, and
APC16. Among the individual subunits of APC/C, APC3, APC6, APC7, APC8, and APC12
exist in a dimer form, while other subunits exist in a monomeric form.
