title: Substrate Recognition by the Cdh1 Destruction Box Receptor Is a General Requirement for APC/CCdh1-mediated Proteolysis.
abstract: The anaphase-promoting complex, or cyclosome (APC/C), is a ubiquitin ligase that selectively targets proteins for degradation in mitosis and the G1 phase and is an important component of the eukaryotic cell cycle control system. How the APC/C specifically recognizes its substrates is not fully understood. Although well characterized degron motifs such as the destruction box (D-box) and KEN-box are commonly found in APC/C substrates, many substrates apparently lack these motifs. A variety of alternative APC/C degrons have been reported, suggesting either that multiple modes of substrate recognition are possible or that our definitions of degron structure are incomplete. We used an in vivo yeast assay to compare the G1 degradation rate of 15 known substrates of the APC/C co-activator Cdh1 under normal conditions and conditions that impair binding of D-box, KEN-box, and the recently identified ABBA motif degrons to Cdh1. The D-box receptor was required for efficient proteolysis of all Cdh1 substrates, despite the absence of canonical D-boxes in many. In contrast, the KEN-box receptor was only required for normal proteolysis of a subset of substrates and the ABBA motif receptor for a single substrate in our system. Our results suggest that binding to the D-box receptor may be a shared requirement for recognition and processing of all Cdh1 substrates.
authors.affiliation: From the Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Liang
authors.initials: L
authors.lastname: Qin
authors.affiliation: From the Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Dimitrius Santiago P S F
authors.initials: DS
authors.lastname: Guimarães
authors.affiliation: From the Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Michael
authors.initials: M
authors.lastname: Melesse
authors.affiliation: From the Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907 mchall@purdue.edu.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Hall
mesh_terms: D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D064200:Cdh1 Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C577583:CDH1 protein, S cerevisiae; D064200:Cdh1 Proteins; D029701:Saccharomyces cerevisiae Proteins; D064173:Anaphase-Promoting Complex-Cyclosome
keywords: APC/CCdh1; Cdh1; KEN box; anaphase-promoting complex; cell cycle; destruction box; protein degradation; protein stability; ubiquitin ligase; ubiquitylation (ubiquitination)