title: Regulation of ubiquitin chain initiation to control the timing of substrate degradation.
abstract: Processive reactions, such as transcription or translation, often proceed through distinct initiation and elongation phases. The processive formation of polymeric ubiquitin chains can accordingly be catalyzed by specialized initiating and elongating E2 enzymes, but the functional significance for this division of labor has remained unclear. Here, we have identified sequence motifs in several substrates of the anaphase-promoting complex (APC/C) that are required for efficient chain initiation by its E2 Ube2C. Differences in the quality and accessibility of these chain initiation motifs can determine the rate of a substrate's degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle. Based on our results, we propose that initiation motifs and their cognate E2s allow E3 enzymes to exert precise temporal control over substrate degradation.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Williamson
authors.forename: Sudeep
authors.initials: S
authors.lastname: Banerjee
authors.forename: Xining
authors.initials: X
authors.lastname: Zhu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Philipp
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Iavarone
authors.forename: Michael
authors.initials: M
authors.lastname: Rape
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D057809:HEK293 Cells; D006801:Humans; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases