Regulation of APC Activity by Phosphorylation and Regulatory Factors

doi:10.1083/jcb.146.4.791

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© The Rockefeller University Press, 0021-9525/1999//791 $5.00
The Journal of Cell Biology, Volume 146, Number 4, , 1999 791-800

Original Article

Regulation of APC Activity by Phosphorylation and Regulatory Factors

Shuji Kotani^a, Hirofumi Tanaka^b, Hideyo Yasuda^b, and Kazuo Todokoro^a

^a Tsukuba Life Science Center, The Institute of Physical and Chemical Research, Tsukuba, Ibaraki 305-0074, Japan
^b School of Life Science, Tokyo University of Pharmacy and Life Science, Hachiooji, Tokyo 192-0355, Japan
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1, Koyadai, Tsukuba, Ibaraki 305-0074, Japan.81-298-36-909081-298-36-9075

todokoro{at}rtc.riken.go.jp

Ubiquitin-dependent proteolysis of Cut2/Pds1 and Cyclin B isrequired for sister chromatid separation and exit from mitosis,respectively. Anaphase-promoting complex/cyclosome (APC) specificallyubiquitinates Cut2/Pds1 at metaphase–anaphase transition,and ubiquitinates Cyclin B in late mitosis and G1 phase. However,the exact regulatory mechanism of substrate-specific activationof mammalian APC with the right timing remains to be elucidated.We found that not only the binding of the activators Cdc20 andCdh1 and the inhibitor Mad2 to APC, but also the phosphorylationof Cdc20 and Cdh1 by Cdc2-Cyclin B and that of APC by Polo-likekinase and cAMP-dependent protein kinase, regulate APC activity.The cooperation of the phosphorylation/dephosphorylation andthe regulatory factors in regulation of APC activity may thuscontrol the precise progression of mitosis.

Key Words: anaphase-promoting complex • Cdc20 • Cdh1 • Mad2 • phosphorylation

1.used in this paper: APC, anaphase promoting complex/cyclosome;MPF, Cdc2-Cyclin B or Cdc2-GST-Cyclin B; pAPC, APC phosphorylatedby pPlk or APlk-activated APC; pCdc20, Cdc20 phosphorylatedby MPF; pCdh1, Cdh1 phosphorylated MPF; PKA, cAMP-dependentprotein kinase; Plk, Polo-like kinase; pPlk, Plk phosphorylatedby MPF

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