Genomes and Genes
Gene Symbol: ELOC
Description: elongin C
Alias: SIII, TCEB1, elongin-C, RNA polymerase II transcription factor SIII subunit C, SIII p15, elongin 15 kDa subunit, transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C), transcription elongation factor B polypeptide 1, transcription elongation factor B subunit 1
- Kamura T, Burian D, Yan Q, Schmidt S, Lane W, Querido E, et al. Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. J Biol Chem. 2001;276:29748-53 pubmed..Taken together, our findings identify MUF1 as a new member of the BC-box family of proteins, and they predict the existence of a larger family of Elongin BC-based E3 ubiquitin ligases. ..
- Li Z, Na X, Wang D, Schoen S, Messing E, Wu G. Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein. J Biol Chem. 2002;277:4656-62 pubmed..Co-immunoprecipitation demonstrates that VDU1 can be recruited into the pVHL-elongin C-elongin B complex...
- Yu Y, Xiao Z, Ehrlich E, Yu X, Yu X. Selective assembly of HIV-1 Vif-Cul5-ElonginB-ElonginC E3 ubiquitin ligase complex through a novel SOCS box and upstream cysteines. Genes Dev. 2004;18:2867-72 pubmed..Therefore, selective assembly with Cul5 versus Cul2 E3 may require protein interfaces besides the SOCS-box-ElonginC interaction. ..
- Donahue J, Vetter M, Mukhtar N, D Aquila R. The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation. Virology. 2008;377:49-53 pubmed publisher..We demonstrate that the failure of the Vif mutant to bind A3G resulted in A3G incorporation into assembling virions with loss of viral infectivity. ..
- Megumi Y, Miyauchi Y, Sakurai H, Nobeyama H, Lorick K, Nakamura E, et al. Multiple roles of Rbx1 in the VBC-Cul2 ubiquitin ligase complex. Genes Cells. 2005;10:679-91 pubmed..Taken together, these results indicate that various mechanisms regulate both the activities and the stability of cullin-based ligases. ..
- Chung A, Guan Y, Yuan Z, Albina J, Chin Y. Ankyrin repeat and SOCS box 3 (ASB3) mediates ubiquitination and degradation of tumor necrosis factor receptor II. Mol Cell Biol. 2005;25:4716-26 pubmed..The data presented here implicate ASB3 as a negative regulator of TNF-R2-mediated cellular responses to TNF-alpha by direct targeting of TNF-R2 for ubiquitination and proteasome-mediated degradation. ..
- Heuzé M, Guibal F, Banks C, Conaway J, Conaway R, Cayre Y, et al. ASB2 is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex. J Biol Chem. 2005;280:5468-74 pubmed..This is a first indication that a member of the ASB protein family, ASB2, is a subunit of an ECS (Elongin C-Cullin-SOCS box)-type E3 ubiquitin ligase complex...
- Mehle A, Goncalves J, Santa Marta M, McPike M, Gabuzda D. Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev. 2004;18:2861-6 pubmed..for degradation by forming an SCF-like E3 ubiquitin ligase containing Cullin 5 and Elongins B and C (Cul5-EloB-EloC) through a novel SOCS (suppressor of cytokine signaling)-box that binds EloC...
- Kibel A, Iliopoulos O, DeCaprio J, Kaelin W. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science. 1995;269:1444-6 pubmed..These results suggest that the tumor suppression function of pVHL may be linked to its ability to bind to Elongin B and C. ..
- Kelsall I, Duda D, Olszewski J, Hofmann K, Knebel A, Langevin F, et al. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 2013;32:2848-60 pubmed publisher..Cumulatively, our work proposes a conserved mechanism of CRL-induced Ariadne RBR ligase activation and further suggests a reciprocal role of this special class of RBRs as regulators of distinct CRLs. ..
- Stebbins C, Kaelin W, Pavletich N. Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science. 1999;284:455-61 pubmed..The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway. ..
- Zadjali F, Pike A, Vesterlund M, Sun J, Wu C, Li S, et al. Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. J Biol Chem. 2011;286:480-90 pubmed publisher..Our data support a role of SOCS6 as a feedback inhibitor of SCF-dependent signaling and provides molecular data to account for target specificity within the SOCS family of ubiquitin ligases. ..
- Reingewertz T, Benyamini H, Lebendiker M, Shalev D, Friedler A. The C-terminal domain of the HIV-1 Vif protein is natively unfolded in its unbound state. Protein Eng Des Sel. 2009;22:281-7 pubmed publisher..Our results provide direct evidence for the unfolded structure of the free Vif CTD and indicate that it may gain structure upon binding its natural ligands. ..
- Kinoshita K, Goryo K, Takada M, Tomokuni Y, Aso T, Okuda H, et al. Ternary complex formation of pVHL, elongin B and elongin C visualized in living cells by a fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy technique. FEBS J. 2007;274:5567-75 pubmedThe tumor suppressor von Hippel-Lindau (VHL) gene product forms a complex with elongin B and elongin C, and acts as a recognition subunit of a ubiquitin E3 ligase...
- Albin J, Harris R. Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics. Expert Rev Mol Med. 2010;12:e4 pubmed publisher..We also summarise, for the first time, current clinical data on the in vivo effects of APOBEC3 proteins, and survey strategies and progress towards developing therapeutics aimed at the APOBEC3-Vif axis. ..
- Kwon S, Kim D, Rhee J, Park J, Kim D, Kim D, et al. ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function. BMC Biol. 2010;8:23 pubmed publisher..ASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential expression and function of ASB9 and ASB9DeltaSOCS may be a key factor in the growth of human cell lines and primary cells. ..
- Debrincat M, Zhang J, Willson T, Silke J, Connolly L, Simpson R, et al. Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation. J Biol Chem. 2007;282:4728-37 pubmed..The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme. ..
- Bergeron J, Huthoff H, Veselkov D, Beavil R, Simpson P, Matthews S, et al. The SOCS-box of HIV-1 Vif interacts with ElonginBC by induced-folding to recruit its Cul5-containing ubiquitin ligase complex. PLoS Pathog. 2010;6:e1000925 pubmed publisher..In particular, in addition to the previously established binding of Vif's BC box to EloC, we report a novel interaction between the conserved Pro-Pro-Leu-Pro motif of Vif and the C-terminal domain of EloB...
- Kario E, Marmor M, Adamsky K, Citri A, Amit I, Amariglio N, et al. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005;280:7038-48 pubmed..Thus, we have characterized a novel function for SOCS5 in regulating EGFR and discuss its potential role in controlling EGFR homeostasis. ..
- Salter J, Lippa G, Belashov I, Wedekind J. Core-binding factor ? increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complex. Biochemistry. 2012;51:8702-4 pubmed publisherHIV-1 Vif masquerades as a receptor for a cellular E3 ligase harboring Elongin B, Elongin C, and Cullin 5 (EloB/C/Cul5) proteins that facilitate degradation of the antiretroviral factor APOBEC3G (A3G)...
- Zhang J, Farley A, Nicholson S, Willson T, Zugaro L, Simpson R, et al. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci U S A. 1999;96:2071-6 pubmed..Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway. ..
- Wang X, Wang X, Zhang H, Lv M, Zuo T, Wu H, et al. Interactions between HIV-1 Vif and human ElonginB-ElonginC are important for CBF-? binding to Vif. Retrovirology. 2013;10:94 pubmed publisher..EloB and EloC were initially reported as positive regulatory subunits of the Elongin (SIII) complex...
- Ohh M, Takagi Y, Aso T, Stebbins C, Pavletich N, Zbar B, et al. Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein. J Clin Invest. 1999;104:1583-91 pubmed..This activity has been linked to its ability to form multimeric complexes that contain elongin C, elongin B, and Cul2...
- Zhang W, Du J, Evans S, Yu Y, Yu X. T-cell differentiation factor CBF-? regulates HIV-1 Vif-mediated evasion of host restriction. Nature. 2011;481:376-9 pubmed publisher..HIV-1 Vif forms an E3 ubiquitin ligase complex with cullin 5 (CUL5), elongin B and elongin C , which promotes the polyubiquitination and degradation of APOBEC3 substrates...
- Hon W, Wilson M, Harlos K, Claridge T, Schofield C, Pugh C, et al. Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL. Nature. 2002;417:975-8 pubmed..This mechanism provides a new focus for development of therapeutic agents to modulate cellular responses to hypoxia. ..
- Brower C, Sato S, Tomomori Sato C, Kamura T, Pause A, Stearman R, et al. Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase. Proc Natl Acad Sci U S A. 2002;99:10353-8 pubmed..Taken together, our findings are consistent with the model that MED8 could function to recruit ubiquitin ligase activity directly to the RNA polymerase II transcriptional machinery. ..
- Tsuchiya H, Iseda T, Hino O. Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product. Cancer Res. 1996;56:2881-5 pubmed..protein(s) that might bind to pVHL using a two-hybrid system and identified seven independent clones, including elongin C, but not elongin B...
- Malim M, Emerman M. HIV-1 accessory proteins--ensuring viral survival in a hostile environment. Cell Host Microbe. 2008;3:388-98 pubmed publisher..Broadly speaking, the HIV-1 accessory proteins modify the local environment within infected cells to ensure viral persistence, replication, dissemination, and transmission. ..
- Kershaw N, Laktyushin A, Nicola N, Babon J. Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates. Growth Factors. 2014;32:1-10 pubmed publisher..SOCS3-induced polyubiquitination was rapid and could proceed through a number of different ubiquitin lysines. SOCS3 catalyzed the ubiquitination of both the IL-6 receptor common chain (gp130) and JAK2. ..
- Mahrour N, Redwine W, Florens L, Swanson S, Martin Brown S, Bradford W, et al. Characterization of Cullin-box sequences that direct recruitment of Cul2-Rbx1 and Cul5-Rbx2 modules to Elongin BC-based ubiquitin ligases. J Biol Chem. 2008;283:8005-13 pubmed publisher..which are substrate recognition subunits of structurally related classes of E3 ubiquitin ligases composed of Elongin C-Elongin B-Cullin 2-Rbx1 (Cul2 ubiquitin ligases) or of Elongin C-Elongin B-Cullin 5-Rbx2 (Cul5 ubiquitin ligases)..
- Bradsher J, Jackson K, Conaway R, Conaway J. RNA polymerase II transcription factor SIII. I. Identification, purification, and properties. J Biol Chem. 1993;268:25587-93 pubmed..This factor, which we designate SIII, has a native molecular mass of approximately 140 kDa and is composed of three polypeptides of 110, 18, and 15 kDa...
- Pause A, Lee S, Worrell R, Chen D, Burgess W, Linehan W, et al. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci U S A. 1997;94:2156-61 pubmed..The VHL protein (pVHL) has been shown to form a stable complex with elongin B and elongin C, two factors that stabilize and activate the transcription elongation factor elongin A...
- Lonergan K, Iliopoulos O, Ohh M, Kamura T, Conaway R, Conaway J, et al. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. Mol Cell Biol. 1998;18:732-41 pubmed..Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein...
- Brower C, Shilatifard A, Mather T, Kamura T, Takagi Y, Haque D, et al. The elongin B ubiquitin homology domain. Identification of Elongin B sequences important for interaction with Elongin C. J Biol Chem. 1999;274:13629-36 pubmed..this report, we show that the Elongin B ubiquitin-like domain is necessary and sufficient for interaction with Elongin C and for positive regulation of Elongin A transcriptional activity...
- Cockman M, Masson N, Mole D, Jaakkola P, Chang G, Clifford S, et al. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem. 2000;275:25733-41 pubmed
- Kuznetsova A, Meller J, Schnell P, Nash J, Ignacak M, Sanchez Y, et al. von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination. Proc Natl Acad Sci U S A. 2003;100:2706-11 pubmed..This interaction is regulated by UV radiation. ..
- Stickle N, Chung J, Klco J, Hill R, Kaelin W, Ohh M. pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development. Mol Cell Biol. 2004;24:3251-61 pubmed..These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis. ..
- Mehle A, Wilson H, Zhang C, Brazier A, McPike M, Pery E, et al. Identification of an APOBEC3G binding site in human immunodeficiency virus type 1 Vif and inhibitors of Vif-APOBEC3G binding. J Virol. 2007;81:13235-41 pubmed
- Luo K, Ehrlich E, Xiao Z, Zhang W, Ketner G, Yu X. Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53. FASEB J. 2007;21:1742-50 pubmed..Therefore, adenovirus E4orf6 molecules represent a novel family of viral BC-box proteins the cellular ancestor of which is as yet unknown. ..
- Pery E, Rajendran K, Brazier A, Gabuzda D. Regulation of APOBEC3 proteins by a novel YXXL motif in human immunodeficiency virus type 1 Vif and simian immunodeficiency virus SIVagm Vif. J Virol. 2009;83:2374-81 pubmed publisher..These results suggest that the YXXL motif in Vif is a potential target for small-molecule inhibitors to block Vif interaction with A3G, A3F, and A3C, and thereby protect cells against HIV-1 infection. ..
- Lu Z, Bergeron J, Atkinson R, Schaller T, Veselkov D, Oregioni A, et al. Insight into the HIV-1 Vif SOCS-box-ElonginBC interaction. Open Biol. 2013;3:130100 pubmed publisher..factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/Cullin5-containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis...
- Babon J, Sabo J, Zhang J, Nicola N, Norton R. The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression. J Mol Biol. 2009;387:162-74 pubmed
- Vesterlund M, Zadjali F, Persson T, Nielsen M, Kessler B, Norstedt G, et al. The SOCS2 ubiquitin ligase complex regulates growth hormone receptor levels. PLoS ONE. 2011;6:e25358 pubmed publisher..The demonstration that SOCS2 is an ubiquitin ligase for the GHR unveils the molecular basis for its physiological actions. ..
- Bullock A, Debreczeni J, Edwards A, Sundstrom M, Knapp S. Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Proc Natl Acad Sci U S A. 2006;103:7637-42 pubmed..9-A crystal structure of the ternary complex of SOCS2 with elongin C and elongin B...
- Wang J, Muntean A, Hess J. ECSASB2 mediates MLL degradation during hematopoietic differentiation. Blood. 2012;119:1151-61 pubmed publisher..Moreover, deletion of the PHD/Bromo region renders MLL fusion proteins resistant to ASB2-mediated degradation and may contribute to leukemogenesis. ..
- Min J, Yang H, Ivan M, Gertler F, Kaelin W, Pavletich N. Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling. Science. 2002;296:1886-9 pubmed..Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling. ..
- Costessi A, Mahrour N, Tijchon E, Stunnenberg R, Stoel M, Jansen P, et al. The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters. EMBO J. 2011;30:3786-98 pubmed publisher..Our results are consistent with a role for the PRAME ubiquitin ligase complex in NFY-mediated transcriptional regulation. ..
- Pause A, Peterson B, Schaffar G, Stearman R, Klausner R. Studying interactions of four proteins in the yeast two-hybrid system: structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein. Proc Natl Acad Sci U S A. 1999;96:9533-8 pubmed..Thus, it seems possible that pVHL/elongin BC/hCUL-2 complex will possess ubiquitin ligase activity targeting specific proteins for degradation by the proteasome. ..
- Reingewertz T, Shalev D, Friedler A. Structural disorder in the HIV-1 Vif protein and interaction-dependent gain of structure. Protein Pept Lett. 2010;17:988-98 pubmed..This ambiguity is likely to be the tenet of structurally unfolded proteins, which have the propensity to adopt a multitude of biologically relevant and active conformations. ..
- Iliopoulos O, Ohh M, Kaelin W. pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation. Proc Natl Acad Sci U S A. 1998;95:11661-6 pubmed..pVHL19, like pVHL30, can bind to elongin B, elongin C, and Hs-Cul2 in coimmunoprecipitation assays and can inhibit the production of hypoxia-inducible proteins such ..
- Thomas J, Matak Vinkovic D, Van Molle I, Ciulli A. Multimeric complexes among ankyrin-repeat and SOCS-box protein 9 (ASB9), ElonginBC, and Cullin 5: insights into the structure and assembly of ECS-type Cullin-RING E3 ubiquitin ligases. Biochemistry. 2013;52:5236-46 pubmed publisher..the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5...
- Li X, Trojer P, Matsumura T, Treisman J, Tanese N. Mammalian SWI/SNF--a subunit BAF250/ARID1 is an E3 ubiquitin ligase that targets histone H2B. Mol Cell Biol. 2010;30:1673-88 pubmed publisher..Here we report that BAF250b complexes purified from mammalian cells contain elongin C (Elo C), a BC box binding component of an E3 ubiquitin ligase...
- Lv W, Liu Z, Jin H, Yu X, Zhang L, Zhang L. Three-dimensional structure of HIV-1 VIF constructed by comparative modeling and the function characterization analyzed by molecular dynamics simulation. Org Biomol Chem. 2007;5:617-26 pubmed..These novel models of VIF and its complex has therefore provided structural information for investigating the function of VIF at the molecular level. ..
- Cai Q, Knight J, Verma S, Zald P, Robertson E. EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog. 2006;2:e116 pubmed..Thus, manipulation of tumor suppressors by LANA potentially provides a favorable environment for progression of KSHV-infected tumor cells. ..