The CRY box: a second APCcdh1‐dependent degron in mammalian cdc20

Cdc20 and cdh1 are coactivators of the anaphase‐promoting complex (APC). APCcdc20 is necessary for the metaphase–anaphase transition and, at the end of mitosis, vertebrate cdc20 itself becomes a target for degradation through KEN‐box‐dependent APCcdh1 activity. By studying the degradation of fluorescent protein chimaeras in mammalian oocytes and early embryos, we found that cdc20 was degraded through two independent degradation signals (degrons), the KEN box and a newly described CRY box. In both oocytes and G1‐stage embryos, the rate of degradation through the CRY box was greater than through the KEN box, although both were mediated by APCcdh1. Thus, mammalian oocytes and embryos have the capacity to recognize two degrons in cdc20.

[1]  A. Hershko,et al.  Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. , 1991, The Journal of biological chemistry.

[2]  P. Jackson,et al.  Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. , 2003, Developmental cell.

[3]  K. Jones,et al.  Degradation of APCcdc20 and APCcdh1 substrates during the second meiotic division in mouse eggs , 2004, Journal of Cell Science.

[4]  M. Brandeis,et al.  Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes , 2002, The EMBO journal.

[5]  Y. Protopopov,et al.  Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20. , 1999, Biochemical and biophysical research communications.

[6]  A. Goldberg,et al.  Selective Inhibitors of the Proteasome-dependent and Vacuolar Pathways of Protein Degradation in Saccharomyces cerevisiae * , 1996, The Journal of Biological Chemistry.

[7]  W. Seufert,et al.  Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC , 2001, The EMBO journal.

[8]  Azad Bonni,et al.  Cdh1-APC Controls Axonal Growth and Patterning in the Mammalian Brain , 2004, Science.

[9]  T. Kishimoto,et al.  Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Kirschner,et al.  Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. , 1998, Molecular cell.

[11]  J. Peters,et al.  Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  K. Jones,et al.  Ca2+ Oscillations Promote APC/C-Dependent Cyclin B1 Degradation during Metaphase Arrest and Completion of Meiosis in Fertilizing Mouse Eggs , 2002, Current Biology.

[13]  Marc W. Kirschner,et al.  Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry , 2004, Nature.

[14]  J. Peters,et al.  Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1 , 2002, The Journal of cell biology.

[15]  A. McDougall,et al.  Sperm-induced calcium oscillations at fertilisation in ascidians are controlled by cyclin B1-dependent kinase activity. , 2000, Development.

[16]  A. Hershko,et al.  Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint. , 2000, Biochemical and biophysical research communications.

[17]  K. Jones,et al.  APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division , 2006, Nature Cell Biology.

[18]  J. Pines,et al.  Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells , 2004, The Journal of cell biology.

[19]  David Pellman,et al.  Activity of the APCCdh1 form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p , 2001, The Journal of cell biology.

[20]  M. Kirschner,et al.  The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. , 2000, Genes & development.

[21]  Sebastian Maurer-Stroh,et al.  TPR Subunits of the Anaphase-Promoting Complex Mediate Binding to the Activator Protein CDH1 , 2003, Current Biology.

[22]  Angelika Amon,et al.  The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis , 1998, Current Biology.

[23]  R. Schultz,et al.  Temporal patterns of gene expression of G1‐S cyclins and cdks during the first and second mitotic cell cycles in mouse embryos , 1996, Molecular reproduction and development.

[24]  M. Johnson,et al.  The relationship between cleavage, DNA replication, and gene expression in the mouse 2-cell embryo. , 1984, Journal of embryology and experimental morphology.