Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Entry into anaphase and exit from mitosis depend on a ubiquitin-protein ligase complex called the anaphase-promoting complex (APC) or cyclosome. At least 12 different subunits were detected in the purified particle from budding yeast, including the previously identified proteins Apc1p, Cdc16p, Cdc23p, Cdc26p, and Cdc27p. Five additional subunits purified in low nanogram amounts were identified by tandem mass spectrometric sequencing. Apc2p, Apc5p, and the RING-finger protein Apc11p are conserved from yeast to humans. Apc2p is similar to the cullin Cdc53p, which is a subunit of the ubiquitin-protein ligase complex SCFCdc4 required for the initiation of DNA replication.
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PMID:Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. 946 14

The anaphase-promoting complex (APC) is a cell cycle-regulated ubiquitin-protein ligase that targets cyclin B, securin and other destruction box containing proteins for proteolysis. Nine APC subunits have been identified in vertebrates and eleven in yeast, but for none of them it is known how they contribute to the catalysis of ubiquitination reactions. Here we report the mass spectrometric identification of CDC26 and of the RING-H2 finger protein APC11 in the human APC. We have expressed these proteins and several other APC subunits in Escherichia coli and have tested their activities in vitro. We find that APC11 alone is sufficient to allow the synthesis of multiubiquitin chains in the presence of E1 and UBC4. These multiubiquitin chains are partly unanchored and partly bound to APC11 itself. APC11 and UBC4 are also able to ubiquitinate securin and cyclin B, but these reactions show a decreased dependency on the destruction box. The integrity of the putative zinc binding RING-H2 finger is required for the ability of APC11 to support ubiquitination reactions. These results suggest that APC11 and UBC4 catalyze the formation of isopeptide bonds in APC-mediated ubiquitination reactions.
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PMID:The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. 1092 56

The anaphase-promoting complex (APC) is a ubiquitin-protein ligase (E3) that targets cell cycle regulators such as cyclin B and securin for degradation. The APC11 subunit functions as the catalytic core of this complex and mediates the transfer of ubiquitin from a ubiquitin-conjugating enzyme (E2) to the substrate. APC11 contains a RING-H2-finger domain, which includes one histidine and seven cysteine residues that coordinate two Zn(2+) ions. We now show that exposure of purified APC11 to H(2)O(2) (0.1 to 1 mM) induced the release of bound zinc as a result of the oxidation of cysteine residues. It also impaired the physical interaction between APC11 and the E2 enzyme Ubc4 as well as inhibited the ubiquitination of cyclin B1 by APC11. The release of HeLa cells from metaphase arrest in the presence of exogenous H(2)O(2) inhibited the ubiquitination of cyclin B1 as well as the degradation of cyclin B1 and securin that were apparent in the absence of H(2)O(2). The presence of H(2)O(2) also blocked the co-immunoprecipitation of Ubc4 with APC11 and delayed the exit of cells from mitosis. Inhibition of APC11 function by H(2)O(2) thus likely contributes to the delay in cell cycle progression through mitosis that is characteristic of cells subjected to oxidative stress.
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PMID:The RING-H2-finger protein APC11 as a target of hydrogen peroxide. 1525 23