The LIG_APCC_Dbox_1 motifs that matched with amino acid residues GRYELAVLE (121-129) functional residues that bind to the Cdh1 and Cdc20
components of APC/C causing protein destruction during the cell cycle in the cytosol.
The APC/C maintains the spindle assembly checkpoint by targeting Cdc20
It was found that expression of TP53 (HR 1.9, p = 31 x [10.sup.-7]) was associated with worse overall survival (OS) for glioma patients, as well as TOP2A (HR 4.4, p = 0), CDK1 (HR 4.8, p = 0), CCNB1 (HR 5.9, p = 0), CDC20
(HR 5.2, p = 0), CCNA2 (HR 5.1, p = 0), NDC80 (HR 5.8, p = 0), AURKA (HR 5.3, p = 0), BIRC5 (HR 5, p = 0), CCNB2 (HR 5.4, p = 0), KIF11 (HR 2.3, p = 15 x [10.sup.-10]), and MAD2L1 (HR 4.4, p = 0), while expression of PHLPP2 (HR 0.41, p = 1.3x [10.sup.-11]), DLG4 (HR 0.59, p = 35 x [10.sup.-5]), and MYC (HR 0.58, p = 2.1 x [10.sup.-5]) was associated with better overall survival (OS) for glioma patients (Figure 3).
When Cdk1 is activated, complex cyclin B/Cdc1 nuclear protein phosphorylation fiber layer will trigger the nuclear membrane decomposition while phosphorylating APC, so that APC can be activated by Cdc20
. APCCdc20 has a biodegradable effect on cyclin A and cyclin B.
The PPI network consisting of induced genes (Figure 3(a)) contained a large cell cycle-related cluster with hubs and nodes related to S-phase (CCNB1 and CCNB2, CCND3, CDC16, MCM3, MCM7, and CDC25) and chromosome separation (PLK1, ANAPC5, 7, CDC20
, and TUBA1A).
The metaphase-anaphase transition is mediated by the ubiquitin protein ligase APC/C  under the control of a network of regulatory factors, including cell division cycle protein 20 (CDC20
), cadherin 1 (CDH1), and MAD2L1.
In addition, mRNA levels of cell cycle exit related genes, Rb, P21, P18, P19, P53, and P45, exhibited a significant increase; in contrast, the cell cycle genes, Cyclin D1, Cyclin D2, Cyclin E, CDK6, E2F1, and CDC20
, were significantly decreased in FGF21 overexpression group (Figure 2(d)).
In the recent reclassification of breast cancers on the basis of copy number expression analysis, the 5q loss is associated with a strong basal-specific signature, including aurora kinase B (AURKB), B-cell CLL/lymphoma 2 (BCL2), BUB1 mitotic checkpoint serine/threonine kinase (BUB1), cell division cycle associated 3 (CDCA3), cell division cycle associated 4 (CDCA4), cell division cycle 20 (CDC20
), cell division cycle 45 (CDC45), checkpoint kinase 1 (CHEK1), forkhead box M1 (FOXM1), histone deacetylase 2 (HDAC2), insulin-like growth factor 1 receptor (IGF1R), kinesin family member 2C (KIF2C), kinesin family member C1 (KIFC1), methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), TTK protein kinase (TTK), and ubiquitin-conjugating enzyme E2C (UBE2C).
PCS and PhS suppressed Cdc20
and Skp2 mRNA expression at 24 hours after treatment.
In addition to E1 and E2 enzymes, APC/C-mediated ubiquitination depends on the activator proteins, Cdc20
or Cdh1 [20-22], with the former regulating the metaphase to anaphase transition through the degradation of securin.
This massive E3 complex, composed of at least 12 subunits, requires binding by Cdh1 or Cdc20
to function, allowing APC activity to be controlled in distinct subcellular compartments by either of these activator proteins .