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Anaphase-promoting complex
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Anaphase-promoting complex : ウィキペディア英語版
Anaphase-promoting complex
''This article refers to the cell-cycle regulatory complex, APC/C. For the tumor suppressor APC, in which mutations lead to colon cancer, see Adenomatous polyposis coli.''
Anaphase-Promoting Complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C still have unknown functions, but are highly conserved.
It was the discovery of the APC/C (and SCF) and their key role in eukaryotic cell reproduction that established once and for all the importance of ubiquitin-mediated proteolysis in eukaryotic cell biology. Once perceived as a system exclusively involved in removing damaged protein from the cell, ubiquitination and subsequent protein degradation by the proteasome is now perceived as a universal regulatory mechanism for signal transduction whose importance approaches that of protein phosphorylation.
In 2014, the APC/C was mapped in 3D at a resolution of less than a nanometre, which also uncovered its secondary structure. Researchers have claimed this finding could transform the understanding of cancer and reveal new binding sites for future cancer drugs.
== Function ==
The APC/C's main function is to trigger the transition from metaphase to anaphase by tagging specific proteins for degradation. The three major targets for degradation by the APC/C are securin and S and M cyclins. Securin releases separase (a protease) after being degraded. The separase triggers the cleavage of cohesin, the protein complex that binds sister chromatids together. During metaphase, sister chromatids are linked by intact cohesin complexes. When securin undergoes ubiquitination by the APC/C and releases separase, which degrades cohesin, sister chromatids become free to move to opposite poles for anaphase. The APC/C also targets the mitotic cyclins for degradation, resulting in the inactivation of M-CDK (mitotic cyclin-dependent kinase) complexes, promoting exit from mitosis and cytokinesis.〔
Unlike the SCF, activator subunits control the APC/C. Cdc20 and Cdh1 are the two activators of particular importance to the cell cycle. These proteins target the APC/C to specific sets of substrates at different times in the cell cycle, thus driving it forward. The APC/C also plays an integral role in maintenance of chromatin metabolism, particularly in G1 and G0, and plays a key role in phosphorylation of H3 through destruction of the aurora A kinase.

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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