Regulation of the cyclin B degradation system by an inhibitor of mitotic proteolysis.
The initiation of anaphase and exit from mitosis depend on the anaphase-promoting complex (APC), which mediates the ubiquitin-dependent proteolysis of anaphase-inhibiting proteins and mitotic cyclins. We have analyzed whether protein phosphatases are required for mitotic APC activation. In Xenopus egg extracts APC activation occurs normally in the presence of protein phosphatase 1 inhibitors, suggesting that the anaphase defects caused by protein phosphatase 1 mutation in several organisms are not due to a failure to activate the APC. Contrary to this, the initiation of mitotic cyclin B proteolysis is prevented by inhibitors of protein phosphatase 2A such as okadaic acid. Okadaic acid induces an activity that inhibits cyclin B ubiquitination. We refer to this activity as inhibitor of mitotic proteolysis because it also prevents the degradation of other APC substrates. A similar activity exists in extracts of Xenopus eggs that are arrested at the second meiotic metaphase by the cytostatic factor activity of the protein kinase mos. In Xenopus eggs, the initiation of anaphase II may therefore be prevented by an inhibitor of APC-dependent ubiquitination.
Vorlaufer
E
E
Research Institute of Molecular Pathology, A-1030 Vienna, Austria.
Peters
J M
JM
D000705:Anaphase / Q000235:genetics; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D008025:Ligases / Q000378:metabolism; D008677:Metaphase / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D010063:Ovum; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D017231:Proto-Oncogene Proteins c-mos / Q000494:pharmacology; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D014981:Xenopus
D019926:Cyclin B; D011480:Protease Inhibitors; D014452:Ubiquitins; D019319:Okadaic Acid; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D017231:Proto-Oncogene Proteins c-mos; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D008025:Ligases