Ubiquitin C Explained

Polyubiquitin-C is a protein encoded by the UBC gene in humans.^{[1] [2] [3]} Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A.^[4]

UBC gene is one of the two stress-regulated polyubiquitin genes (UBB and UBC) in mammals. It plays a key role in maintaining cellular ubiquitin levels under stress conditions.^{[5] [6]} Defects of UBC gene could lead to mid-gestation embryonic lethality.

Structure

Gene

UBC gene is located at chromosome 12q24.3, consisting of 2 exons. The promoter of the UBC gene contains putative heat shock elements (HSEs), which mediates UBC induction upon stress. UBC gene differs from UBB gene in the number of Ub coding units they contain.^[5] Nine to ten Ub units were in the UBC gene.

Protein

In polyubiquitin-C, the C-terminus of a given ubiquitin molecule is covalently conjugated to either the N-terminal residue or one of seven lysine residues of another ubiquitin molecule.^[7] Different linking of ubiquitin chains results in distinct conformations. There are 8 linkage types of polyubiquitin-C, and each type possesses the linkage-dependent dynamics and a linkage-specific conformation.^{[8] [9]}

Function

The diversity of polyubiquitin-C means that ubiquitylation contributes to the regulation of many cellular events. Polyubiquitin-C doesn’t activate the heat-shock response, but it plays a key role in sustaining the response. UBC gene transcription is induced during stress and provides extra ubiquitin necessary to remove damaged/unfolded proteins.^{[6] [10]} Polyubiquitin-C has important role in diverse biological processes, such as innate immunity, DNA repair and kinase activity.^{[11] [12] [13]} Unanchored polyubiquitin-C are also key signaling molecules that connect and coordinate the proteasome and autophagy to eliminate toxic protein aggregates.^[14]

Clinical significance

Loss of a single UBC allele has no apparent phenotype, while homozygous deletion of UBC gene leads to mid-gestation embryonic lethality due to a defect in fetal liver development, as well as a delay in cell-cycle progression and increased susceptibility to cellular stress.^[6] It is also reported that homozygous deletion of UBC gene in mouse embryonic fibroblasts will cause decreased cellular Ub level and reduced viability under oxidative stress.^[15]

Interactions

Polyubiquitin-C has been shown to interact with:

• BIRC2,^{[16] [17]}
• BSG,^[18]
• CDC2,
• CFAP298,^[19]
• E2F1,^[20]
• EGFR,^{[21] [22] [23]}
• HDAC3,^[24]
• HIF1A,^{[25] [26] [27]}
• IRAK1,^{[28] [29]}
• KIAA0753.^[30]
• MARK4,
• MDM2,^{[31] [32] [33]}
• NDUFA3,^[34]
• NFE2L2,^{[35] [36]}
• NOTCH1,^[37]
• NUAK1,^[38]
• OPRK1,^[39]
• P53,^{[21] [31] [32] [33] [40] [41] [42] [43]}
• PCNA^{[44] [45] [46]}
• PARK2,^{[47] [48]}
• RIPK1,^{[49] [50] [51]}
• RPS6KB1,^[52]
• S100A10,^[53]
• SCNN1A,^{[54] [55]}
• SCNN1G,^{[54] [55]}
• SFPQ,^[56]
• SMAD3,^{[57] [58]}
• SMURF2,^{[59] [60]}
• SP1,^[61]
• TRAF6,^{[62] [63] [64] [65] [66]} and
• THRA.^[24]

Further reading

• Mazzé FM, Degrève L . The role of viral and cellular proteins in the budding of human immunodeficiency virus . Acta Virologica . 50 . 2 . 75–85 . 2006 . 16808324 .
• Kanayama H, Tanaka K, Aki M, Kagawa S, Miyaji H, Satoh M, Okada F, Sato S, Shimbara N, Ichihara A . Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells . Cancer Research . 51 . 24 . 6677–85 . December 1991 . 1660345 .
• Baker RT, Board PG . Unequal crossover generates variation in ubiquitin coding unit number at the human UbC polyubiquitin locus . American Journal of Human Genetics . 44 . 4 . 534–42 . April 1989 . 2564731 . 1715567 .
• Einspanier R, Sharma HS, Scheit KH . Cloning and sequence analysis of a cDNA encoding poly-ubiquitin in human ovarian granulosa cells . Biochemical and Biophysical Research Communications . 147 . 2 . 581–7 . September 1987 . 2820408 . 10.1016/0006-291X(87)90970-3 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Nenoi M, Mita K, Ichimura S, Cartwright IL, Takahashi E, Yamauchi M, Tsuji H . Heterogeneous structure of the polyubiquitin gene UbC of HeLa S3 cells . Gene . 175 . 1–2 . 179–85 . October 1996 . 8917096 . 10.1016/0378-1119(96)00145-X .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Nenoi M, Mita K, Ichimura S, Kawano A . Higher frequency of concerted evolutionary events in rodents than in man at the polyubiquitin gene VNTR locus . Genetics . 148 . 2 . 867–76 . February 1998 . 10.1093/genetics/148.2.867 . 9504932 . 1459823 .
• Ott DE, Coren LV, Copeland TD, Kane BP, Johnson DG, Sowder RC, Yoshinaka Y, Oroszlan S, Arthur LO, Henderson LE . Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus . Journal of Virology . 72 . 4 . 2962–8 . April 1998 . 9525617 . 109742 . 10.1128/JVI.72.4.2962-2968.1998.
• Kim NS, Yamaguchi T, Sekine S, Saeki M, Iwamuro S, Kato S . Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its in vitro translation product . Journal of Biochemistry . 124 . 1 . 35–9 . July 1998 . 9644242 . 10.1093/oxfordjournals.jbchem.a022093 .
• Schubert U, Ott DE, Chertova EN, Welker R, Tessmer U, Princiotta MF, Bennink JR, Krausslich HG, Yewdell JW . Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2 . Proceedings of the National Academy of Sciences of the United States of America . 97 . 24 . 13057–62 . November 2000 . 11087859 . 27177 . 10.1073/pnas.97.24.13057 . 2000PNAS...9713057S . free .
• Strack B, Calistri A, Accola MA, Palu G, Gottlinger HG . A role for ubiquitin ligase recruitment in retrovirus release . Proceedings of the National Academy of Sciences of the United States of America . 97 . 24 . 13063–8 . November 2000 . 11087860 . 27178 . 10.1073/pnas.97.24.13063 . 2000PNAS...9713063S . free .
• Ott DE, Coren LV, Chertova EN, Gagliardi TD, Schubert U . Ubiquitination of HIV-1 and MuLV Gag . Virology . 278 . 1 . 111–21 . December 2000 . 11112487 . 10.1006/viro.2000.0648 . free .
• Strack B, Calistri A, Göttlinger HG . Late assembly domain function can exhibit context dependence and involves ubiquitin residues implicated in endocytosis . Journal of Virology . 76 . 11 . 5472–9 . June 2002 . 11991975 . 137019 . 10.1128/JVI.76.11.5472-5479.2002 .
• Huang L, Feng L, Yang L, Zhou W, Zhao S, Li C . Screen and identification of proteins interacting with ADAM19 cytoplasmic tail . Molecular Biology Reports . 29 . 3 . 317–23 . September 2002 . 12463424 . 10.1023/A:1020409217215 . 22611084 .
• Ott DE, Coren LV, Sowder RC, Adams J, Schubert U . Retroviruses have differing requirements for proteasome function in the budding process . Journal of Virology . 77 . 6 . 3384–93 . March 2003 . 12610113 . 149504 . 10.1128/JVI.77.6.3384-3393.2003 .
• Evans PC, Smith TS, Lai MJ, Williams MG, Burke DF, Heyninck K, Kreike MM, Beyaert R, Blundell TL, Kilshaw PJ . A novel type of deubiquitinating enzyme . The Journal of Biological Chemistry . 278 . 25 . 23180–6 . June 2003 . 12682062 . 10.1074/jbc.M301863200 . free .

Notes and References

1. Board PG, Coggan M, Baker RT, Vuust J, Webb GC . Localization of the human UBC polyubiquitin gene to chromosome band 12q24.3 . Genomics . 12 . 4 . 639–42 . April 1992 . 1315303 . 10.1016/0888-7543(92)90287-3 .
2. Marinovic AC, Zheng B, Mitch WE, Price SR . Ubiquitin (UbC) expression in muscle cells is increased by glucocorticoids through a mechanism involving Sp1 and MEK1 . The Journal of Biological Chemistry . 277 . 19 . 16673–81 . May 2002 . 11872750 . 10.1074/jbc.M200501200 . free .
3. Web site: Entrez Gene: UBC ubiquitin C.
4. Kimura Y, Tanaka K . Regulatory mechanisms involved in the control of ubiquitin homeostasis . Journal of Biochemistry . 147 . 6 . 793–8 . June 2010 . 20418328 . 10.1093/jb/mvq044 . free .
5. Wiborg O, Pedersen MS, Wind A, Berglund LE, Marcker KA, Vuust J . The human ubiquitin multigene family: some genes contain multiple directly repeated ubiquitin coding sequences . The EMBO Journal . 4 . 3 . 755–9 . March 1985 . 2988935 . 554252. 10.1002/j.1460-2075.1985.tb03693.x .
6. Ryu KY, Maehr R, Gilchrist CA, Long MA, Bouley DM, Mueller B, Ploegh HL, Kopito RR . The mouse polyubiquitin gene UbC is essential for fetal liver development, cell-cycle progression and stress tolerance . The EMBO Journal . 26 . 11 . 2693–706 . June 2007 . 17491588 . 10.1038/sj.emboj.7601722 . 1888680.
7. Komander D, Rape M . The ubiquitin code . Annual Review of Biochemistry . 81 . 203–29 . 2012 . 22524316 . 10.1146/annurev-biochem-060310-170328 . 30693177 .
8. Ye Y, Blaser G, Horrocks MH, Ruedas-Rama MJ, Ibrahim S, Zhukov AA, Orte A, Klenerman D, Jackson SE, Komander D . Ubiquitin chain conformation regulates recognition and activity of interacting proteins . Nature . 492 . 7428 . 266–70 . December 2012 . 23201676 . 10.1038/nature11722 . 3605796. 2012Natur.492..266Y .
9. Castañeda CA, Kashyap TR, Nakasone MA, Krueger S, Fushman D . Unique structural, dynamical, and functional properties of k11-linked polyubiquitin chains . Structure . 21 . 7 . 1168–81 . July 2013 . 23823328 . 10.1016/j.str.2013.04.029 . 3802530.
10. Tsirigotis M, Zhang M, Chiu RK, Wouters BG, Gray DA . Sensitivity of mammalian cells expressing mutant ubiquitin to protein-damaging agents . The Journal of Biological Chemistry . 276 . 49 . 46073–8 . December 2001 . 11598140 . 10.1074/jbc.M109023200 . free.
11. Rajsbaum R, Versteeg GA, Schmid S, Maestre AM, Belicha-Villanueva A, Martínez-Romero C, Patel JR, Morrison J, Pisanelli G, Miorin L, Laurent-Rolle M, Moulton HM, Stein DA, Fernandez-Sesma A, tenOever BR, García-Sastre A . Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response . Immunity . 40 . 6 . 880–95 . June 2014 . 24882218 . 10.1016/j.immuni.2014.04.018 . 4114019.
12. Rajsbaum R, García-Sastre A . Virology. Unanchored ubiquitin in virus uncoating . Science . 346 . 6208 . 427–8 . October 2014 . 25342790 . 10.1126/science.1261509 . 28504276 .
13. Pickart CM, Fushman D . Polyubiquitin chains: polymeric protein signals . Current Opinion in Chemical Biology . 8 . 6 . 610–6 . December 2004 . 15556404 . 10.1016/j.cbpa.2004.09.009 .
14. Hao R, Nanduri P, Rao Y, Panichelli RS, Ito A, Yoshida M, Yao TP . Proteasomes activate aggresome disassembly and clearance by producing unanchored ubiquitin chains . Molecular Cell . 51 . 6 . 819–28 . September 2013 . 24035499 . 10.1016/j.molcel.2013.08.016 . 3791850.
15. Ryu HW, Ryu KY . Quantification of oxidative stress in live mouse embryonic fibroblasts by monitoring the responses of polyubiquitin genes . Biochemical and Biophysical Research Communications . 404 . 1 . 470–5 . January 2011 . 21144824 . 10.1016/j.bbrc.2010.12.004 .
16. Didelot C, Lanneau D, Brunet M, Bouchot A, Cartier J, Jacquel A, Ducoroy P, Cathelin S, Decologne N, Chiosis G, Dubrez-Daloz L, Solary E, Garrido C . Interaction of heat-shock protein 90 beta isoform (HSP90 beta) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation . Cell Death and Differentiation . 15 . 5 . 859–66 . May 2008 . 18239673 . 10.1038/cdd.2008.5 . free .
17. Sekine K, Takubo K, Kikuchi R, Nishimoto M, Kitagawa M, Abe F, Nishikawa K, Tsuruo T, Naito M . Small molecules destabilize cIAP1 by activating auto-ubiquitylation . The Journal of Biological Chemistry . 283 . 14 . 8961–8 . April 2008 . 18230607 . 10.1074/jbc.M709525200 . free .
18. Wang WJ, Li QQ, Xu JD, Cao XX, Li HX, Tang F, Chen Q, Yang JM, Xu ZD, Liu XP . Interaction between CD147 and P-glycoprotein and their regulation by ubiquitination in breast cancer cells . Chemotherapy . 54 . 4 . 291–301 . 18689982 . 10.1159/000151225 . 2008. 7260048 .
19. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP . Systematic and quantitative assessment of the ubiquitin-modified proteome . Molecular Cell . 44 . 2 . 325–40 . October 2011 . 21906983 . 3200427 . 10.1016/j.molcel.2011.08.025 .
20. Zhou F, Zhang L, Wang A, Song B, Gong K, Zhang L, Hu M, Zhang X, Zhao N, Gong Y . The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation . The Journal of Biological Chemistry . 283 . 21 . 14506–15 . May 2008 . 18367454 . 10.1074/jbc.M706136200 . free .
21. Sehat B, Andersson S, Girnita L, Larsson O . Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis . Cancer Research . 68 . 14 . 5669–77 . July 2008 . 18632619 . 10.1158/0008-5472.CAN-07-6364 .
22. Pennock S, Wang Z . A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation . Molecular and Cellular Biology . 28 . 9 . 3020–37 . May 2008 . 18316398 . 2293090 . 10.1128/MCB.01809-07 .
23. Umebayashi K, Stenmark H, Yoshimori T . Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation . Molecular Biology of the Cell . 19 . 8 . 3454–62 . August 2008 . 18508924 . 2488299 . 10.1091/mbc.E07-10-0988 .
24. Tan F, Lu L, Cai Y, Wang J, Xie Y, Wang L, Gong Y, Xu BE, Wu J, Luo Y, Qiang B, Yuan J, Sun X, Peng X . Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells . Proteomics . 8 . 14 . 2885–96 . July 2008 . 18655026 . 10.1002/pmic.200700887 . 25586938 .
25. André H, Pereira TS . Identification of an alternative mechanism of degradation of the hypoxia-inducible factor-1alpha . The Journal of Biological Chemistry . 283 . 43 . 29375–84 . October 2008 . 18694926 . 2662024 . 10.1074/jbc.M805919200 . free .
26. Park YK, Ahn DR, Oh M, Lee T, Yang EG, Son M, Park H . Nitric oxide donor, (+/-)-S-nitroso-N-acetylpenicillamine, stabilizes transactive hypoxia-inducible factor-1alpha by inhibiting von Hippel-Lindau recruitment and asparagine hydroxylation . Molecular Pharmacology . 74 . 1 . 236–45 . July 2008 . 18426857 . 10.1124/mol.108.045278 . 31675735 .
27. Kim BY, Kim H, Cho EJ, Youn HD . Nur77 upregulates HIF-alpha by inhibiting pVHL-mediated degradation . Experimental & Molecular Medicine . 40 . 1 . 71–83 . February 2008 . 18305400 . 2679322 . 10.3858/emm.2008.40.1.71 .
28. Xiao H, Qian W, Staschke K, Qian Y, Cui G, Deng L, Ehsani M, Wang X, Qian YW, Chen ZJ, Gilmour R, Jiang Z, Li X . Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation . The Journal of Biological Chemistry . 283 . 21 . 14654–64 . May 2008 . 18326498 . 2386918 . 10.1074/jbc.M706931200 . free .
29. Windheim M, Stafford M, Peggie M, Cohen P . Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase . Molecular and Cellular Biology . 28 . 5 . 1783–91 . March 2008 . 18180283 . 2258775 . 10.1128/MCB.02380-06 .
30. KIAA0753 Gene - GeneCards | K0753 Protein | K0753 Antibody, (available at https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA0753).
31. Ivanchuk SM, Mondal S, Rutka JT . p14ARF interacts with DAXX: effects on HDM2 and p53 . Cell Cycle . 7 . 12 . 1836–50 . June 2008 . 18583933 . 10.4161/cc.7.12.6025 . free .
32. Song MS, Song SJ, Kim SY, Oh HJ, Lim DS . The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex . The EMBO Journal . 27 . 13 . 1863–74 . July 2008 . 18566590 . 2486425 . 10.1038/emboj.2008.115 .
33. Yang W, Dicker DT, Chen J, El-Deiry WS . CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2 . Cell Cycle . 7 . 5 . 670–82 . March 2008 . 18382127 . 10.4161/cc.7.5.5701 . free .
34. Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C . A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles . Molecular & Cellular Proteomics . 10 . 10 . M111.013284 . October 2011 . 21890473 . 3205876 . 10.1074/mcp.M111.013284 . free .
35. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M, Hirohashi S . Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy . Proceedings of the National Academy of Sciences of the United States of America . 105 . 36 . 13568–73 . September 2008 . 18757741 . 2533230 . 10.1073/pnas.0806268105 . 2008PNAS..10513568S . free .
36. Patel R, Maru G . Polymeric black tea polyphenols induce phase II enzymes via Nrf2 in mouse liver and lungs . Free Radical Biology & Medicine . 44 . 11 . 1897–911 . June 2008 . 18358244 . 10.1016/j.freeradbiomed.2008.02.006 .
37. Chastagner P, Israël A, Brou C . AIP4/Itch regulates Notch receptor degradation in the absence of ligand . PLOS ONE . 3 . 7 . e2735 . 18628966 . 2444042 . 10.1371/journal.pone.0002735 . Wölfl . Stefan . 2008 . 2008PLoSO...3.2735C . free .
38. Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR . Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains . The Biochemical Journal . 411 . 2 . 249–60 . April 2008 . 18254724 . 10.1042/BJ20080067 . 13038944 .
39. Li JG, Haines DS, Liu-Chen LY . Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation . Molecular Pharmacology . 73 . 4 . 1319–30 . April 2008 . 18212250 . 3489932 . 10.1124/mol.107.042846 .
40. Han JM, Park BJ, Park SG, Oh YS, Choi SJ, Lee SW, Hwang SK, Chang SH, Cho MH, Kim S . AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53 . Proceedings of the National Academy of Sciences of the United States of America . 105 . 32 . 11206–11 . August 2008 . 18695251 . 2516205 . 10.1073/pnas.0800297105 . 2008PNAS..10511206H . free .
41. Abe Y, Oda-Sato E, Tobiume K, Kawauchi K, Taya Y, Okamoto K, Oren M, Tanaka N . Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2 . Proceedings of the National Academy of Sciences of the United States of America . 105 . 12 . 4838–43 . March 2008 . 18359851 . 2290789 . 10.1073/pnas.0712216105 . 2008PNAS..105.4838A . free .
42. Zhang Z, Zhang R . Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation . The EMBO Journal . 27 . 6 . 852–64 . March 2008 . 18309296 . 2265109 . 10.1038/emboj.2008.25 .
43. Dohmesen C, Koeppel M, Dobbelstein M . Specific inhibition of Mdm2-mediated neddylation by Tip60 . Cell Cycle . 7 . 2 . 222–31 . January 2008 . 18264029 . 10.4161/cc.7.2.5185 . 8023403 .
44. Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K . Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks . Proceedings of the National Academy of Sciences of the United States of America . 105 . 34 . 12411–6 . August 2008 . 18719106 . 2518831 . 10.1073/pnas.0805685105 . 2008PNAS..10512411M . free .
45. Unk I, Hajdú I, Fátyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L . Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination . Proceedings of the National Academy of Sciences of the United States of America . 105 . 10 . 3768–73 . March 2008 . 18316726 . 2268824 . 10.1073/pnas.0800563105 . 2008PNAS..105.3768U . free .
46. Brun J, Chiu R, Lockhart K, Xiao W, Wouters BG, Gray DA . hMMS2 serves a redundant role in human PCNA polyubiquitination . BMC Molecular Biology . 9 . 24 . 18284681 . 2263069 . 10.1186/1471-2199-9-24 . 2008 . free .
47. Yu F, Zhou J . Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress . Neuroscience Letters . 440 . 1 . 4–8 . July 2008 . 18541373 . 10.1016/j.neulet.2008.05.052 . 2169911 .
48. Kawahara K, Hashimoto M, Bar-On P, Ho GJ, Crews L, Mizuno H, Rockenstein E, Imam SZ, Masliah E . alpha-Synuclein aggregates interfere with Parkin solubility and distribution: role in the pathogenesis of Parkinson disease . The Journal of Biological Chemistry . 283 . 11 . 6979–87 . March 2008 . 18195004 . 10.1074/jbc.M710418200 . free .
49. Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA . cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination . Molecular Cell . 30 . 6 . 689–700 . June 2008 . 18570872 . 10.1016/j.molcel.2008.05.014 . free .
50. Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D . c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation . The Journal of Biological Chemistry . 283 . 36 . 24295–9 . September 2008 . 18621737 . 3259840 . 10.1074/jbc.C800128200 . free .
51. Liao W, Xiao Q, Tchikov V, Fujita K, Yang W, Wincovitch S, Garfield S, Conze D, El-Deiry WS, Schütze S, Srinivasula SM . CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation . Current Biology . 18 . 9 . 641–9 . May 2008 . 18450452 . 2587165 . 10.1016/j.cub.2008.04.017 .
52. Panasyuk G, Nemazanyy I, Filonenko V, Gout I . Ribosomal protein S6 kinase 1 interacts with and is ubiquitinated by ubiquitin ligase ROC1 . Biochemical and Biophysical Research Communications . 369 . 2 . 339–43 . May 2008 . 18279656 . 10.1016/j.bbrc.2008.02.016 .
53. He KL, Deora AB, Xiong H, Ling Q, Weksler BB, Niesvizky R, Hajjar KA . Endothelial cell annexin A2 regulates polyubiquitination and degradation of its binding partner S100A10/p11 . The Journal of Biological Chemistry . 283 . 28 . 19192–200 . July 2008 . 18434302 . 2443646 . 10.1074/jbc.M800100200 . free .
54. Boulkroun S, Ruffieux-Daidié D, Vitagliano JJ, Poirot O, Charles RP, Lagnaz D, Firsov D, Kellenberger S, Staub O . Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3 . American Journal of Physiology. Renal Physiology . 295 . 4 . F889–900 . October 2008 . 18632802 . 10.1152/ajprenal.00001.2008 .
55. Raikwar NS, Thomas CP . Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel . American Journal of Physiology. Renal Physiology . 294 . 5 . F1157–65 . May 2008 . 18322022 . 2424110 . 10.1152/ajprenal.00339.2007 .
56. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
57. Stolfi C, Fina D, Caruso R, Caprioli F, Fantini MC, Rizzo A, Sarra M, Pallone F, Monteleone G . Mesalazine negatively regulates CDC25A protein expression and promotes accumulation of colon cancer cells in S phase . Carcinogenesis . 29 . 6 . 1258–66 . June 2008 . 18495657 . 10.1093/carcin/bgn122 . free .
58. Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF . Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling . Genes & Development . 22 . 1 . 106–20 . January 2008 . 18172167 . 2151009 . 10.1101/gad.1590908 .
59. Carpentier I, Coornaert B, Beyaert R . Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation . Biochemical and Biophysical Research Communications . 374 . 4 . 752–7 . October 2008 . 18671942 . 10.1016/j.bbrc.2008.07.103 .
60. Lee YS, Han JM, Son SH, Choi JW, Jeon EJ, Bae SC, Park YI, Kim S . AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2 . Biochemical and Biophysical Research Communications . 371 . 3 . 395–400 . July 2008 . 18448069 . 10.1016/j.bbrc.2008.04.099 .
61. Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ . Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process . Journal of Molecular Biology . 380 . 5 . 869–85 . July 2008 . 18572193 . 10.1016/j.jmb.2008.05.043 .
62. Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM . Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies . Cell . 134 . 4 . 668–78 . August 2008 . 18724939 . 10.1016/j.cell.2008.07.039 . 3955385 . free .
63. Conze DB, Wu CJ, Thomas JA, Landstrom A, Ashwell JD . Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation . Molecular and Cellular Biology . 28 . 10 . 3538–47 . May 2008 . 18347055 . 2423148 . 10.1128/MCB.02098-07 .
64. Ma Q, Zhou L, Shi H, Huo K . NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation . Cellular Signalling . 20 . 6 . 1044–51 . June 2008 . 18299187 . 10.1016/j.cellsig.2008.01.015 .
65. Chen L, Dong W, Zou T, Ouyang L, He G, Liu Y, Qi Y . Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6 . FEBS Letters . 582 . 19 . 2843–9 . August 2008 . 18634786 . 10.1016/j.febslet.2008.07.014 . 27700566 . free .
66. Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG . The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL . The Journal of Biological Chemistry . 283 . 36 . 24871–80 . September 2008 . 18617513 . 2529010 . 10.1074/jbc.M802749200 . free .