Structural highlights
Function
[CDH1_YEAST] Activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C). During telophase and in the subsequent G1 phase of the cell cycle, recognizes and binds proteins containing a destruction box (D-box) and an additional degradation signal termed the KEN box including ASE1, CDC20, the B-type cyclins CLB2 and CLB3, the polo-like kinase CDC5 and HSL1, and recruits them in a C-box-dependent manner to the APC/C for ubiquitination and subsequent proteolysis. Required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1. Probably is the target of a BUB2-dependent spindle checkpoint pathway.[1] [2] [3] [ACM1_YEAST] Negative regulator of GDH1, the activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C), and which is required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1.[4]
Publication Abstract from PubMed
The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs-predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor.
Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex.,He J, Chao WC, Zhang Z, Yang J, Cronin N, Barford D Mol Cell. 2013 May 22. pii: S1097-2765(13)00329-8. doi:, 10.1016/j.molcel.2013.04.024. PMID:23707760[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alexandru G, Zachariae W, Schleiffer A, Nasmyth K. Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage. EMBO J. 1999 May 17;18(10):2707-21. PMID:10329618 doi:10.1093/emboj/18.10.2707
- ↑ Schwab M, Neutzner M, Mocker D, Seufert W. Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. EMBO J. 2001 Sep 17;20(18):5165-75. PMID:11566880 doi:10.1093/emboj/20.18.5165
- ↑ Huang JN, Park I, Ellingson E, Littlepage LE, Pellman D. Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p. J Cell Biol. 2001 Jul 9;154(1):85-94. PMID:11448992
- ↑ Martinez JS, Jeong DE, Choi E, Billings BM, Hall MC. Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting complex/cyclosome in budding yeast. Mol Cell Biol. 2006 Dec;26(24):9162-76. Epub 2006 Oct 9. PMID:17030612 doi:10.1128/MCB.00603-06
- ↑ He J, Chao WC, Zhang Z, Yang J, Cronin N, Barford D. Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex. Mol Cell. 2013 May 22. pii: S1097-2765(13)00329-8. doi:, 10.1016/j.molcel.2013.04.024. PMID:23707760 doi:10.1016/j.molcel.2013.04.024
