Regulation of APC activity by phosphorylation and regulatory factors.
Ubiquitin-dependent proteolysis of Cut2/Pds1 and Cyclin B is required for sister chromatid separation and exit from mitosis, respectively. Anaphase-promoting complex/cyclosome (APC) specifically ubiquitinates Cut2/Pds1 at metaphase-anaphase transition, and ubiquitinates Cyclin B in late mitosis and G1 phase. However, the exact regulatory mechanism of substrate-specific activation of mammalian APC with the right timing remains to be elucidated. We found that not only the binding of the activators Cdc20 and Cdh1 and the inhibitor Mad2 to APC, but also the phosphorylation of Cdc20 and Cdh1 by Cdc2-Cyclin B and that of APC by Polo-like kinase and cAMP-dependent protein kinase, regulate APC activity. The cooperation of the phosphorylation/dephosphorylation and the regulatory factors in regulation of APC activity may thus control the precise progression of mitosis.
Kotani
S
S
Tsukuba Life Science Center, The Institute of Physical and Chemical Research, Tsukuba, Ibaraki 305-0074, Japan.
Tanaka
H
H
Yasuda
H
H
Todokoro
K
K
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D015703:Antigens, CD; D016203:CDC2 Protein Kinase / Q000378:metabolism; D015820:Cadherins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D064246:Mad2 Proteins; D016200:Maturation-Promoting Factor / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009687:Nuclear Proteins; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D016203:CDC2 Protein Kinase; D015820:Cadherins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D019926:Cyclin B; D005656:Fungal Proteins; D008025:Ligases; D064246:Mad2 Proteins; D016200:Maturation-Promoting Factor; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins; D000097869:Polo-Like Kinase 1; C577495:CDC20 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C513384:CDH1 protein, human; C081185:CKS1 protein, S cerevisiae; C103136:Cut2 protein, S pombe; C577695:MAD2 protein, S cerevisiae; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; C051655:Suc1 protein, S pombe; C577696:mad2 protein, S pombe