APC/C degron instances
Figure 1. Sequence logo of the KEN box degron
A relative frequency sequence logo constructed by subtracting the expected frequency of an amino acid from the observed frequency of an amino acid. A positive score suggests that a residues is enriched , a negative score sugests that a residue is depleted, and score of zero suggest that a residue is occurring at the expected frequency. The logo was constructed from all experimentally characterised KEN box degrons.
References
(1) "Modulation of the mitotic regulatory network by APC-dependent destruction of the Cdh1 inhibitor Acm1." Enquist-Newman M, Sullivan M, Morgan DO. Mol. Cell. 2008 May;30 (4):437-46
(2) "Pseudosubstrate inhibition of the anaphase-promoting complex by Acm1: regulation by proteolysis and Cdc28 phosphorylation." Ostapenko D, Burton JL, Wang R, Solomon MJ. Mol. Cell. Biol.. 2008 Aug;28 (15):4653-64
(3) "Unique D box and KEN box sequences limit ubiquitination of Acm1 and promote pseudosubstrate inhibition of the anaphase-promoting complex." Choi E, Dial JM, Jeong DE, Hall MC. J. Biol. Chem.. 2008 Aug;283 (35):23701-10
(4) "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 Jun;50 (5):649-60
(5) "Alk1 and Alk2 are two new cell cycle-regulated haspin-like proteins in budding yeast." Nespoli A, Vercillo R, di Nola L, Diani L, Giannattasio M, Plevani P, Muzi-Falconi M. Cell Cycle. 2006 Jul;5 (13):1464-71
(6) "Mutually dependent degradation of Ama1p and Cdc20p terminates APC/C ubiquitin ligase activity at the completion of meiotic development in yeast." Tan GS, Lewandowski R, Mallory MJ, Strich R, Cooper KF. Cell Div. 2013 ;8 (1):9
(7) "Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes." Colombo SL, Palacios-Callender M, Frakich N, De Leon J, Schmitt CA, Boorn L, Davis N, Moncada S. Proc. Natl. Acad. Sci. U.S.A.. 2010 Nov;107 (44):18868-73
(8) "Centromeric cohesion is protected twice at meiosis, by SHUGOSHINs at anaphase I and by PATRONUS at interkinesis." Cromer L, Jolivet S, Horlow C, Chelysheva L, Heyman J, De Jaeger G, Koncz C, De Veylder L, Mercier R. Curr. Biol.. 2013 Nov;23 (21):2090-9
(9) "APC/Fizzy-Related targets Aurora-A kinase for proteolysis." Castro A, Arlot-Bonnemains Y, Vigneron S, Labbé JC, Prigent C, Lorca T. EMBO Rep.. 2002 May;3 (5):457-62
(10) "Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit." Littlepage LE, Ruderman JV. Genes Dev.. 2002 Sep;16 (17):2274-85
(11) "Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property." Nguyen HG, Chinnappan D, Urano T, Ravid K. Mol. Cell. Biol.. 2005 Jun;25 (12):4977-92
(12) "APC/C(Cdh1) targets brain-specific kinase 2 (BRSK2) for degradation via the ubiquitin-proteasome pathway." Li R, Wan B, Zhou J, Wang Y, Luo T, Gu X, Chen F, Yu L. PLoS ONE. 2012 ;7 (9):e45932
(13) "KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome." Qi W, Yu H. J. Biol. Chem.. 2007 Feb;282 (6):3672-9
(14) "BubR1 blocks substrate recruitment to the APC/C in a KEN-box-dependent manner." Lara-Gonzalez P, Scott MI, Diez M, Sen O, Taylor SS. J. Cell. Sci.. 2011 Dec;124 (Pt 24):4332-45
(15) "Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1." Elowe S, Dulla K, Uldschmid A, Li X, Dou Z, Nigg EA. J. Cell. Sci.. 2010 Jan;123 (Pt 1):84-94
(16) "Structural analysis of human Cdc20 supports multisite degron recognition by APC/C." Tian W, Li B, Warrington R, Tomchick DR, Yu H, Luo X. Proc. Natl. Acad. Sci. U.S.A.. 2012 Nov;109 (45):18419-24
(17) "Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint." Burton JL, Solomon MJ. Genes Dev.. 2007 Mar;21 (6):655-67
(18) "Ama1p-activated anaphase-promoting complex regulates the destruction of Cdc20p during meiosis II." Tan GS, Magurno J, Cooper KF. Mol. Biol. Cell. 2011 Feb;22 (3):315-26
(19) "The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1." Pfleger CM, Kirschner MW. Genes Dev.. 2000 Mar;14 (6):655-65
(20) "Dual mode of degradation of Cdc25 A phosphatase." Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta GF. EMBO J.. 2002 Sep;21 (18):4875-84
(21) "Differential mitotic degradation of the CDC25B phosphatase variants." Kieffer I, Lorenzo C, Dozier C, Schmitt E, Ducommun B. Oncogene. 2007 Dec;26 (57):7847-58
(22) "Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway." Chen F, Zhang Z, Bower J, Lu Y, Leonard SS, Ding M, Castranova V, Piwnica-Worms H, Shi X. Proc. Natl. Acad. Sci. U.S.A.. 2002 Feb;99 (4):1990-5
(23) "CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis." Mailand N, Diffley JF. Cell. 2005 Sep;122 (6):915-26
(23) "CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis." Mailand N, Diffley JF. Cell. 2005 Sep;122 (6):915-26
(24) "Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC." Ayad NG, Rankin S, Murakami M, Jebanathirajah J, Gygi S, Kirschner MW. Cell. 2003 Apr;113 (1):101-13
(25) "Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates." Rankin S, Ayad NG, Kirschner MW. Mol. Cell. 2005 Apr;18 (2):185-200
(26) "Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F." Gurden MD, Holland AJ, van Zon W, Tighe A, Vergnolle MA, Andres DA, Spielmann HP, Malumbres M, Wolthuis RM, Cleveland DW, Taylor SS. J. Cell. Sci.. 2010 Feb;123 (Pt 3):321-30
(27) "Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence." Hildebrandt ER, Hoyt MA. Mol. Biol. Cell. 2001 Nov;12 (11):3402-16
(28) "CKAP2 is a spindle-associated protein degraded by APC/C-Cdh1 during mitotic exit." Seki A, Fang G. J. Biol. Chem.. 2007 May;282 (20):15103-13
(29) "Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors." Yumoto T, Nakadate K, Nakamura Y, Sugitani Y, Sugitani-Yoshida R, Ueda S, Sakakibara S. PLoS ONE. 2013 ;8 (11):e79895
(30) "Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle." Amon A, Irniger S, Nasmyth K. Cell. 1994 Jul;77 (7):1037-50
(31) "Phosphorylation-triggered CUEDC2 degradation promotes UV-induced G1 arrest through APC/C(Cdh1) regulation." Zhang WN, Zhou J, Zhou T, Li AL, Wang N, Xu JJ, Chang Y, Man JH, Pan X, Li T, Li WH, Mu R, Liang B, Chen L, Jin BF, Xia Q, Gong WL, Zhang XM, Wang L, Li HY. Proc. Natl. Acad. Sci. U.S.A.. 2013 Jul;110 (27):11017-22
(32) "Fission yeast Cut2 required for anaphase has two destruction boxes." Funabiki H, Yamano H, Nagao K, Tanaka H, Yasuda H, Hunt T, Yanagida M. EMBO J.. 1997 Oct;16 (19):5977-87
(33) "Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding." Ramachandran V, Matzkies M, Dienemann A, Sprenger F. Cell Cycle. 2007 Jan;6 (2):171-81
(34) "Regulated degradation of spindle assembly factors by the anaphase-promoting complex." Song L, Rape M. Mol. Cell. 2010 May;38 (3):369-82
(35) "5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal." Ghoshal K, Datta J, Majumder S, Bai S, Kutay H, Motiwala T, Jacob ST. Mol. Cell. Biol.. 2005 Jun;25 (11):4727-41
(36) "Constitutive instability of muscle regulatory factor Myf5 is distinct from its mitosis-specific disappearance, which requires a D-box-like motif overlapping the basic domain." Lindon C, Albagli O, Domeyne P, Montarras D, Pinset C. Mol. Cell. Biol.. 2000 Dec;20 (23):8923-32
(37) "Sororin cooperates with the acetyltransferase Eco2 to ensure DNA replication-dependent sister chromatid cohesion." Lafont AL, Song J, Rankin S. Proc. Natl. Acad. Sci. U.S.A.. 2010 Nov;107 (47):20364-9
(38) "Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1)." Lai F, Hu K, Wu Y, Tang J, Sang Y, Cao J, Kang T. Chin J Cancer. 2012 Sep;31 (9):440-8
(39) "Amyloid β-induced FOXRED2 mediates neuronal cell death via inhibition of proteasome activity." Shim S, Lee W, Chung H, Jung YK. Cell. Mol. Life Sci.. 2011 Jun;68 (12):2115-27
(40) "OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM." Cromer L, Heyman J, Touati S, Harashima H, Araou E, Girard C, Horlow C, Wassmann K, Schnittger A, De Veylder L, Mercier R. PLoS Genet.. 2012 ;8 (7):e1002865
(41) "Anaphase-promoting complex/cyclosome-mediated proteolysis of Ams2 in the G1 phase ensures the coupling of histone gene expression to DNA replication in fission yeast." Trickey M, Fujimitsu K, Yamano H. J. Biol. Chem.. 2013 Jan;288 (2):928-37
(42) "D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p." Burton JL, Solomon MJ. Genes Dev.. 2001 Sep;15 (18):2381-95
(43) "APC/C is an essential regulator of centrosome clustering." Drosopoulos K, Tang C, Chao WC, Linardopoulos S. Nat Commun. 2014 ;5 ():3686
(44) "Human Kid is degraded by the APC/C(Cdh1) but not by the APC/C(Cdc20)." Feine O, Zur A, Mahbubani H, Brandeis M. Cell Cycle. 2007 Oct;6 (20):2516-23
(45) "Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway." Castro A, Vigneron S, Bernis C, Labbé JC, Lorca T. Mol. Cell. Biol.. 2003 Jun;23 (12):4126-38
(45) "Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway." Castro A, Vigneron S, Bernis C, Labbé JC, Lorca T. Mol. Cell. Biol.. 2003 Jun;23 (12):4126-38
(46) "Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint." King EM, van der Sar SJ, Hardwick KG. PLoS ONE. 2007 ;2 (4):e342
(47) "A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast." Kimata Y, Trickey M, Izawa D, Gannon J, Yamamoto M, Yamano H. Dev. Cell. 2008 Mar;14 (3):446-54
(48) "APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box." Hames RS, Wattam SL, Yamano H, Bacchieri R, Fry AM. EMBO J.. 2001 Dec;20 (24):7117-27
(49) "Cell cycle-dependent expression of centrosomal ninein-like protein in human cells is regulated by the anaphase-promoting complex." Wang Y, Zhan Q. J. Biol. Chem.. 2007 Jun;282 (24):17712-9
(50) "NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity." Li L, Zhou Y, Sun L, Xing G, Tian C, Sun J, Zhang L, He F. Cell. Signal.. 2007 Oct;19 (10):2046-55
(51) "Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate." Emanuele MJ, Ciccia A, Elia AE, Elledge SJ. Proc. Natl. Acad. Sci. U.S.A.. 2011 Jun;108 (24):9845-50
(52) "The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1." Herrero-Mendez A, Almeida A, Fernández E, Maestre C, Moncada S, Bolaños JP. Nat. Cell Biol.. 2009 Jun;11 (6):747-52
(53) "Increased concentrations of fructose 2,6-bisphosphate contribute to the Warburg effect in phosphatase and tensin homolog (PTEN)-deficient cells." Cordero-Espinoza L, Hagen T. J. Biol. Chem.. 2013 Dec;288 (50):36020-8
(54) "Drosophila securin destruction involves a D-box and a KEN-box and promotes anaphase in parallel with Cyclin A degradation." Leismann O, Lehner CF. J. Cell. Sci.. 2003 Jun;116 (Pt 12):2453-60
(55) "Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis." Zur A, Brandeis M. EMBO J.. 2001 Feb;20 (4):792-801
(56) "Arabidopsis ULTRAVIOLET-B-INSENSITIVE4 maintains cell division activity by temporal inhibition of the anaphase-promoting complex/cyclosome." Heyman J, Van den Daele H, De Wit K, Boudolf V, Berckmans B, Verkest A, Alvim Kamei CL, De Jaeger G, Koncz C, De Veylder L. Plant Cell. 2011 Dec;23 (12):4394-410
(57) "The anaphase-promoting complex/cyclosome controls repair and recombination by ubiquitylating Rhp54 in fission yeast." Trickey M, Grimaldi M, Yamano H. Mol. Cell. Biol.. 2008 Jun;28 (12):3905-16
(58) "Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis." Chabes AL, Pfleger CM, Kirschner MW, Thelander L. Proc. Natl. Acad. Sci. U.S.A.. 2003 Apr;100 (7):3925-9
(59) "Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle." Strnad P, Leidel S, Vinogradova T, Euteneuer U, Khodjakov A, Gönczy P. Dev. Cell. 2007 Aug;13 (2):203-13
(60) "Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human Sgo1." Karamysheva Z, Diaz-Martinez LA, Crow SE, Li B, Yu H. J. Biol. Chem.. 2009 Jan;284 (3):1772-80
(61) "Proteome-wide discovery of evolutionary conserved sequences in disordered regions." Nguyen Ba AN, Yeh BJ, van Dyk D, Davidson AR, Andrews BJ, Weiss EL, Moses AM. Sci Signal. 2012 Mar;5 (215):rs1
(62) "STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification." Arquint C, Nigg EA. Curr. Biol.. 2014 Feb;24 (4):351-60
(63) "Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway." Ke PY, Chang ZF. Mol. Cell. Biol.. 2004 Jan;24 (2):514-26
(64) "Identification of anaphase promoting complex substrates in S. cerevisiae." Ostapenko D, Burton JL, Solomon MJ. PLoS ONE. 2012 ;7 (9):e45895
(65) "Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit." Stewart S, Fang G. Mol. Cell. Biol.. 2005 Dec;25 (23):10516-27
(66) "Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry." Huang X, Summers MK, Pham V, Lill JR, Liu J, Lee G, Kirkpatrick DS, Jackson PK, Fang G, Dixit VM. Mol. Cell. 2011 May;42 (4):511-23
(67) "Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest." Harley ME, Allan LA, Sanderson HS, Clarke PR. EMBO J.. 2010 Jul;29 (14):2407-20