Regulated degradation of spindle assembly factors by the anaphase-promoting complex.
The ubiquitin ligase anaphase-promoting complex (APC/C) is essential for cell division in all eukaryotes. Loss of APC/C activity arrests cells at metaphase and results in severe aberrations of the mitotic spindle, but how the APC/C regulates spindle formation is not understood. Here, we report that the APC/C promotes the ubiquitination and degradation of four proteins required for Ran-dependent spindle assembly: Bard1, Hmmr, HURP, and NuSAP. Among these substrates, HURP and NuSAP can be degraded during spindle formation when the spindle checkpoint is active. Their degradation requires additional layers of regulation, and both SAFs are only degraded after being released from their inhibitor importin beta by Ran(GTP). Our findings reveal a tightly regulated mechanism by which the APC/C and the GTPase Ran control the abundance of active spindle assembly factors to achieve the accurate formation of the mitotic spindle.
Song
Ling
L
Department of Molecular Cell Biology, University of California, Berkeley, 16 Barker Hall, Berkeley, CA 94720, USA.
Rape
Michael
M
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
C465041:DLGAP5 protein, human; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D028961:beta Karyopherins; C098946:hyaluronan-mediated motility receptor; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D020931:ran GTP-Binding Protein
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