Anaphase-promoting complex 491067 220722374 2008-06-21T07:09:02Z DOI bot 6652755 Citation maintenance. Initiated by [[User:Fconaway|Fconaway]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Anaphase-promoting complex''' ('''APC''') is a complex of several [[protein]]s which is activated during [[mitosis]] to initiate [[anaphase]]. The APC is an E3 [[ubiquitin ligase]] that marks target proteins for degradation by the 26S [[proteasome]]. The irreversibility of proteolysis is utilized by cells to give the cell cycle directionality. The APC indirectly triggers the degradation of [[cohesin]], the protein complex that binds sister [[chromatid]]s together. During [[metaphase]] sister chromatids are linked by intact cohesin complexes. The [[spindle checkpoint]] inhibits the APC until all sister-kinetochores are attached to opposite poles of the [[mitotic spindle]]. When all kinetochores are properly attached the [[spindle checkpoint]] is silenced and the APC becomes active. The activated APC then targets [[securin]] for degradation. Securin inhibits a [[protease]] called [[separase]], which cleaves [[cohesin]]s allowing anaphase onset. The APC also targets the [[mitotic cyclin]]s for degradation, resulting in the inactivation of M-CdK (mitotic cyclin dependent kinase) complexes, promoting exit from [[mitosis]]. There are two mitotic specificity factors for the APC, which target different sets of proteins and are regulated differently: Cdc20 and Cdh1. Cdc20 binds to APC early in mitosis to activate it. It is not clear what kinases phosphorylate and activate the Cdc20-APC complex. It is known that M-Cdk is required for the activity of these kinases, although there is a significant delay between M-CdK activation and the activation of the Cdc20-APC complex. The molecular basis of the delay is unknown, but is believed to involve the key to the correct timing of anaphase initiation. The APC 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. <ref name=MBoC>{{ cite book | year = 2002 | title = Molecular Biology of the Cell | editor = Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter | publisher = Garland Science | chapter = Ch17 | edition = 4th }}</ref> Note that while activation of Cdc20-APC requires M-Cdk, the complex is also responsible for breaking the cyclin to deactivate M-CdK. CdK has an N-terminal destruction box (D-box). APC brings together an E2 [[ubiquitin-conjugating enzyme]] and the D-box rather than being an intermediate covalent carrier<ref>{{cite journal |author=King RW, Deshaies RJ, Peters JM, Kirschner MW. | title=How proteolysis drives the cell cycle | journal=Science | volume=274 | pages=1652–1659 | doi=10.1126/science.274.5293.1652 | year=1996 | pmid=8939846}}{{Entrez Pubmed|8939846}}</ref>. Thus, as M-CdK and Cdc20-APC concentrations rise during the early part of mitosis, they are controlled by [[negative feedback]]. Cdh1, is activated later to form a Cdh1-APC complex to drive exit from mitosis. M-CdK inhibits Cdh1 by phosphorylation and therefore Cdh1-APC only increases in late mitosis, after Cdc-APC has initiated destruction of M-cyclin. It was the discovery of the APC (and [[SCF complex|SCF]]) and the key role that they have 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]]. ==References== <references/> * Zachariae, W. and K. Nasmyth (1999) Whose end is destruction: cell division and the anaphase-promoting complex. [http://www.genesdev.org/cgi/content/full/13/16/2039 Genes Dev. 1999; 13(16): 2039-58] (<span style="color: red;">Review</span>) * J. Wade Harper, Janet L. Burton, and Mark J. Solomon (2002): The anaphase-promoting complex: it's not just for mitosis any more. [http://www.genesdev.org/cgi/content/full/16/17/2179 Genes Dev. 2002; 16(17):2179-206] (<span style="color: red;">Review</span>) ==External links== * {{MeshName|anaphase-promoting+complex}} {{Ligases}} [[Category:Mitosis]] [[Category:Proteins]] [[de:Anaphase-promoting complex]]