Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all eukaryotes. In particular, the APC/C (anaphase promoting complex or cyclosome) is a master ubiquitin protein ligase (E3) that targets PDS1/SECURIN and cyclin B for degradation allowing sister chromatid separation and exit from mitosis, respectively. Interestingly, it has been found that the APC/C remains active in differentiated neurons in which the E3 ligase regulates axon growth, neuronal survival and synaptic functions. However, despite these recent findings, the role of APC/C in differentiated cells and the regulation of its activity beyond cell division is still poorly understood. Here, we investigate the activity and function of APC/C in the model plant Arabidopsis thaliana. We used cyclin reporter constructs to follow APC/C activity during plant development and found that this E3 ligase remains active in most post-mitotic plant cells. Strikingly, hypomorphic mutant lines, in which the APC/C activity is reduced, exhibited several developmental abnormalities, including defects in cotyledon vein patterning and internode elongation leading to a characteristic broomhead-like phenotype. Histological analyses revealed an increased amount of vascular tissue, most notably xylem and lignified sclerenchyma, indicating a role for APC/C in plant vasculature development and organization.
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PMID:The APC/C E3 ligase remains active in most post-mitotic Arabidopsis cells and is required for proper vasculature development and organization. 1933 65

The largest E3 ubiquitin-ligase complex, known as anaphase-promoting complex/cyclosome (APC/C), regulates the proteolysis of cell cycle regulators such as CYCLIN B and SECURIN that are essential for sister-chromatid separation and exit from mitosis. Despite its importance, the role of APC/C in plant cells and the regulation of its activity during cell division remain poorly understood. Here, the Arabidopsis thaliana APC/C subunit APC10 was characterized and shown to functionally complement an apc10 yeast mutant. The APC10 protein was located in specific nuclear bodies, most probably resulting from its association with the proteasome complex. An apc10 Arabidopsis knockout mutant strongly impaired female gametogenesis. Surprisingly, constitutive overexpression of APC10 enhanced leaf size. Through kinematic analysis, the increased leaf size was found to be due to enhanced rates of cell division during the early stages of leaf development and, at the molecular level, by increased APC/C activity as measured by an amplification of the proteolysis rate of the mitotic cyclin, CYCB1;1.
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PMID:The APC/C subunit 10 plays an essential role in cell proliferation during leaf development. 2171

Tumour suppressors safeguard the fidelity of the mitotic checkpoint by transcriptional regulation of genes that encode components of the mitotic checkpoint complex (MCC). Here we report a new role for the tumour suppressor and transcription factor, WT1, in the mitotic checkpoint. We show that WT1 regulates the MCC by directly interacting with the spindle assembly checkpoint protein, MAD2. WT1 colocalizes with MAD2 during mitosis and preferentially binds to the functionally active, closed-conformer, C-MAD2. Furthermore, WT1 associates with the MCC containing MAD2, BUBR1 and CDC20, resulting in prolonged inhibition of the anaphase-promoting complex/cyclosome (APC/C) and delayed degradation of its substrates SECURIN and CYCLIN B1. Strikingly, RNA interference-mediated depletion of WT1 leads to enhanced turnover of SECURIN, decreased lag time to anaphase and defects in chromosome segregation. Our findings identify WT1 as a regulator of the mitotic checkpoint and chromosomal stability.
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PMID:WT1 interacts with MAD2 and regulates mitotic checkpoint function. 2523 65