Disease relevance of apc

• Moreover, the specific APC mutations associated in colon cancer indicate the possibility that the tumor selects for certain truncated forms of APC that partially retain its function, namely, inhibition of beta-catenin [1].

High impact information on apc

• Since activation of separase by the anaphase-promoting complex (APC/C) is supposedly not required for meiosis I in Xenopus oocytes, it has been suggested that animal cells might resolve chiasmata by a separase-independent mechanism related to the so-called "prophase pathway" that removes cohesin from chromosome arms during mitosis [2].
• Here we identify XErp1, a novel Plx1-regulated inhibitor of APC/C activity, and we demonstrate that XErp1 is required to prevent anaphase onset in CSF-arrested Xenopus egg extract [3].
• The anaphase-promoting complex/cyclosome (APC/C) is a highly regulated ubiquitin-ligase that triggers anaphase onset and mitotic exit by targeting securin and mitotic cyclins for destruction [3].
• These results suggest that dephosphorylation of serine 53 during mitotic exit could control the timing of Aur-A destruction, allowing recognition of both the A box and D box by Cdh1-activated APC/C [4].
• Destruction boxes mark cyclin B and other proteins degraded in mitosis for ubiquitination by the anaphase-promoting complex (APC/C) [5].

Biological context of apc

• The predominant pattern of APC mutations may provide synergistic oncogenic effects that promote colorectal tumorigenesis: the optimal signaling for cell survival and renewal, disrupted cell adhesion, chromosomal instability, and altered asymmetric division of stem cells [1].
• We propose that lack of microtubule binding in cancer-associated mutations of APC may contribute to defects in the assembly of mitotic spindles and lead to missegregation of chromosomes [6].
• Mutations in the adenomatous polyposis coli (APC) protein occur early in colon cancer and correlate with chromosomal instability [6].
• Our results confirm and extend models in which inhibition of GSK3 has two synergistic effects: (1) reduction of APC phosphorylation and loss of affinity for beta-catenin and (2) reduction of beta-catenin phosphorylation and consequent loss of its affinity for the SCF ubiquitin ligase complex [7].
• Dishevelled thus stabilizes beta-catenin, which can dissociate from the APC/axin complex and participate in transcriptional activation [7].

Anatomical context of apc

• These data indicate that the APC protein plays a role in the formation of spindles that is dependent on its effect on microtubules [6].
• These data suggest that APC is important for centrosomally driven spindle formation, which was confirmed by our finding that APC depletion reduced the size of asters nucleated from isolated centrosomes [6].
• CSF is thought to suppress cyclin B degradation through the inhibition of the anaphase-promoting complex/cyclosome (APC/C)-Cdc20 while cyclin B synthesis continues in unfertilized eggs [8].

Associations of apc with chemical compounds

• Fertilization triggers a transient increase in cytosolic free Ca(2+), which leads to CSF inactivation and ubiquitin-dependent cyclin destruction through the anaphase promoting complex or cyclosome (APC/C) [9].

Other interactions of apc

• We provide evidence that APC mutations are selected not based on the maximal level of beta-catenin but rather based on distinct state of activity that appears to be optimal for the tissue-specific tumorigenesis [1].
• The ubiquitin-dependent beta-catenin degradation in extracts displays a biochemical requirement for axin, GSK3, and APC [7].
• However, plakoglobin may have other activities: it is expressed in both desmosomal junctions in association with desmogleins and the cytoplasm in conjunction with APC, and previous work suggests it may act in a dorsal signalling pathway when overexpressed in Xenopus embryos [10].

References