Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity.
Metaphase-to-anaphase transition is a fundamental step in cell cycle progression where duplicated sister-chromatids segregate to the future daughter cells. The anaphase-promoting complex/cyclosome (APC/C) is a highly regulated ubiquitin-ligase that triggers anaphase onset and mitotic exit by targeting securin and mitotic cyclins for destruction. It was previously shown that the Xenopus polo-like kinase Plx1 is essential to activate APC/C upon release from cytostatic factor (CSF) arrest in Xenopus egg extract. Although the mechanism by which Plx1 regulates APC/C activation remained unclear, the existence of a putative APC/C inhibitor was postulated whose activity would be neutralized by Plx1 upon CSF release. Here we identify XErp1, a novel Plx1-regulated inhibitor of APC/C activity, and we demonstrate that XErp1 is required to prevent anaphase onset in CSF-arrested Xenopus egg extract. Inactivation of XErp1 leads to premature APC/C activation. Conversely, addition of excess XErp1 to Xenopus egg extract prevents APC/C activation. Plx1 phosphorylates XErp1 in vitro at a site that targets XErp1 for degradation upon CSF release. Thus, our data lead to a model of APC/C activation in Xenopus egg extract in which Plx1 targets the APC/C inhibitor XErp1 for degradation.
Schmidt
Andreas
A
Chemical Biology, Independent Research Group, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany.
Duncan
Peter I
PI
Rauh
Nadine R
NR
Sauer
Guido
G
Fry
Andrew M
AM
Nigg
Erich A
EA
Mayer
Thomas U
TU
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D017931:DNA Primers; D044783:F-Box Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors*; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000097869:Polo-Like Kinase 1
D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; D017931:DNA Primers; D044783:F-Box Proteins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D043743:Ubiquitin-Protein Ligase Complexes; D029867:Xenopus Proteins; C498166:FBXO43 protein, Xenopus; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1