PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression.
Ubiquitin-mediated proteolysis is the key to cell cycle control. Anaphase-promoting complex/cyclosome (APC) is a ubiquitin ligase that targets cyclin B and factors regulating sister chromatid separation for proteolysis by the proteasome and, consequently, regulates metaphase-anaphase transition and exit from mitosis. Here we report that Cdc2-cyclin B-activated Polo-like kinase (Plk) specifically phosphorylates at least three components of APC and activates APC to ubiquitinate cyclin B in the in vitro-reconstituted system. Conversely, protein kinase A (PKA) phosphorylates two subunits of APC but suppresses APC activity. PKA is superior to Plk in its regulation of APC, and Plk activity peaks whereas PKA activity is falling at metaphase. These results indicate that Plk and PKA regulate mitosis progression by controlling APC activity.
Kotani
S
S
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Japan.
Tugendreich
S
S
Fujii
M
M
Jorgensen
P M
PM
Watanabe
N
N
Hoog
C
C
Hieter
P
P
Todokoro
K
K
D016475:3T3 Cells / Q000166:cytology / Q000201:enzymology; D000705:Anaphase / Q000502:physiology*; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004586:Electrophoresis; D004789:Enzyme Activation / Q000502:physiology; D006639:Histidine; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D000090204:Mesothelin; D008677:Metaphase / Q000502:physiology; D051379:Mice; D008938:Mitosis / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D014452:Ubiquitins / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064173:Anaphase-Promoting Complex-Cyclosome; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D006639:Histidine; D016200:Maturation-Promoting Factor; D000090204:Mesothelin; D009097:Multienzyme Complexes; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D014452:Ubiquitins; D000097869:Polo-Like Kinase 1; C577396:Cdc16 protein, mouse; C000715528:Msln protein, mouse