Preventing fatal destruction: inhibitors of the anaphase-promoting complex in meiosis.
The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitin-ligase whose major functions in the cell cycle are the initiation of sister chromatid separation and the inactivation of cyclin-dependent kinases. This complex is also essential for meiosis, a specialized form of the cell cycle characterized by two consecutive rounds of chromosome segregation. To ensure a proper meiotic cell cycle, the activity of APC/C needs to be tightly controlled. It is now evident that inhibitors of APC/C play pivotal roles to avert its untimely activation. During prophase I, this ubiquitin-ligase must be kept inactive to prevent precocious sister chromatid separation. Studies in yeast showed that this inhibition is mediated by a specific subunit of the complex. Accurate chromosome segregation in meiosis I depends on spindle checkpoint proteins such as Mad2 which delay APC/C activation in response to an erroneous spindle attachment of chromosomes. Additional APC/C antagonists are known to block complete cyclin destruction between meiosis I and II, thereby ensuring that cyclin dependent kinases remain active and that DNA replication does not occur. Inhibitors of APC/C also mediate the cytostatic factor induced metaphase II arrest of oocytes. This review highlights the current knowledge about the role and relevance of these diverse regulators of the meiotic APC/C.
Institute of Microbiology and Genetics,Georg-August-University, Göttingen, Germany. sirnige@gwdg.de
Stefan
S
Irniger
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D020090:Chromosome Segregation / Q000235:genetics; D008540:Meiosis; D008677:Metaphase / Q000502:physiology; D011418:Prophase / Q000502:physiology; D016196:S Phase / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome