Gene Symbol: Cul2
Description: cullin 2
Alias: cullin-2, CUL-2, testis secretory sperm-binding protein Li 238E
Species: human
Products:     Cul2

Top Publications

  1. Knauth K, Bex C, Jemth P, Buchberger A. Renal cell carcinoma risk in type 2 von Hippel-Lindau disease correlates with defects in pVHL stability and HIF-1alpha interactions. Oncogene. 2006;25:370-7 pubmed
    ..We propose that this residual ubiquitin ligase activity is sufficient to suppress renal cell carcinogenesis in vivo. ..
  2. Yang X, Menon S, Lykke Andersen K, Tsuge T, Di Xiao -, Wang X, et al. The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase progression via deneddylation of SCF Cul1. Curr Biol. 2002;12:667-72 pubmed
    ..The polyclonal antibodies against CSN2 but not other CSN subunits cause accumulation of neddylated Cul1/Cul2 in HeLa cell extract, indicating that CSN2 is essential in cullin deneddylation...
  3. Lyapina S, Cope G, Serino G, Tsuge T, Zhou C, Wolf D, et al. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001;292:1382-5 pubmed
  4. Min K, Kwon M, Park H, Park Y, Yoon S, Yoon J. CAND1 enhances deneddylation of CUL1 by COP9 signalosome. Biochem Biophys Res Commun. 2005;334:867-74 pubmed
    ..Our data suggest that enhancement of CSN-mediated deneddylation by CAND1 may contribute to its function as a positive regulator of SCFs in vivo. ..
  5. 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
    ..was found to function as an adaptor that links these BC-box proteins to a module composed of Cullin family members Cul2 or Cul5 and RING-H2 finger protein Rbx1 to reconstitute a family of E3 ubiquitin ligases that activate ..
  6. Min K, Hwang J, Lee J, Park Y, Tamura T, Yoon J. TIP120A associates with cullins and modulates ubiquitin ligase activity. J Biol Chem. 2003;278:15905-10 pubmed
    ..These results suggest that TIP120A functions as a negative regulator of SCF E3 ubiquitin ligases and may modulate other cullin ligases in a similar fashion. ..
  7. Bandau S, Knebel A, Gage Z, Wood N, Alexandru G. UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1? accumulation. BMC Biol. 2012;10:36 pubmed publisher
    ..mediates p97 interaction with the transcription factor HIF1? that is actively ubiquitylated in normoxic cells by a CUL2-based E3 ligase, CRL2...
  8. Litterman N, Ikeuchi Y, Gallardo G, O Connell B, Sowa M, Gygi S, et al. An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning. PLoS Biol. 2011;9:e1001060 pubmed publisher
  9. Maine G, Mao X, Komarck C, Burstein E. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007;26:436-47 pubmed
    ..of NF-kappaB subunits through its interaction with a multimeric ubiquitin ligase containing Elongins B and C, Cul2 and SOCS1 (ECS(SOCS1))...

More Information


  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
    ..Recently, the VHL-Elongin BC complex was found to interact with a module composed of Cullin family member Cul2 and RING-H2 finger protein Rbx1 to reconstitute a novel E3 ubiquitin ligase that activates ubiquitylation by the E2 ..
  2. Sufan R, Ohh M. Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complex. Neoplasia. 2006;8:956-63 pubmed
    ECV is an E3 ubiquitin ligase complex, which is composed of elongins B and C, Rbx1, Cul2, and the substrate-conferring von Hippel-Lindau (VHL) tumor-suppressor protein that targets the catalytic alpha subunit of hypoxia-inducible factor (..
  3. Dias D, Dolios G, Wang R, Pan Z. CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proc Natl Acad Sci U S A. 2002;99:16601-6 pubmed
    ..Strikingly, CUL7 selectively interacts with Skp1.Fbx29 but not with Skp1.betaTRCP2 or Skp1.Skp2. Thus, CUL7 may define a previously uncharacterized, Fbx29-mediated, and ubiquitin-dependent proteolysis pathway. ..
  4. Chew E, Hagen T. Substrate-mediated regulation of cullin neddylation. J Biol Chem. 2007;282:17032-40 pubmed
    ..These ligases are composed of one of six mammalian cullin homologs (Cul1, Cul2, Cul3, Cul4a, Cul4b, and Cul5), the Ring finger containing protein Roc1/Rbx1, and cullin homolog-specific adaptor ..
  5. Yan Q, Kamura T, Cai Y, Jin J, Ivan M, Mushegian A, et al. Identification of Elongin C and Skp1 sequences that determine Cullin selection. J Biol Chem. 2004;279:43019-26 pubmed
    ..serves as the substrate recognition subunit, which is linked by the adaptor protein Elongin C to a heterodimeric Cul2/Rbx1 module that activates ubiquitylation of target proteins by the E2 ubiquitin-conjugating enzyme Ubc5...
  6. Kamura T, Sato S, Iwai K, Czyzyk Krzeska M, Conaway R, Conaway J. Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc Natl Acad Sci U S A. 2000;97:10430-5 pubmed
    ..Our findings provide new insight into the function of the VHL tumor suppressor protein, and they provide a foundation for future investigations of the mechanisms underlying VHL regulation of oxygen-dependent gene expression. ..
  7. 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
  8. 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. To understand this process in greater detail, we performed a series of in vitro binding assays using pVHL, elongin ..
  9. Kamura T, Conrad M, Yan Q, Conaway R, Conaway J. The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2. Genes Dev. 1999;13:2928-33 pubmed
    ..subunit of the related SCF (Skp1-Cdc53/Cul1-F-box protein) and von Hippel-Lindau (VHL) tumor suppressor (elongin BC-Cul2-VHL) E3 ubiquitin ligase complexes, where it functions as a component of Cdc53/Rbx1 and Cul2/Rbx1 modules that ..
  10. 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. ..
  11. Wada H, Yeh E, Kamitani T. Identification of NEDD8-conjugation site in human cullin-2. Biochem Biophys Res Commun. 1999;257:100-5 pubmed
  12. 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
    ..Rbx1/ROC1/Hrt1, a RING finger protein, functions as an important component of the cullin-containing SCF and VBC-Cul2 ligases...
  13. 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
    ..BAF250b was found to have a BC box motif, associate with Elo C in a BC box-dependent manner, and, together with cullin 2 and Roc1, assemble into an E3 ubiquitin ligase...
  14. Zheng J, Yang X, Harrell J, Ryzhikov S, Shim E, Lykke Andersen K, et al. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell. 2002;10:1519-26 pubmed
    ..Our data suggest that CAND1 regulates the formation of the SCF complex, and its dissociation from CUL1 is coupled with the incorporation of F box proteins into the SCF complex, causing their destabilization. ..
  15. Kamura T, Brower C, Conaway R, Conaway J. A molecular basis for stabilization of the von Hippel-Lindau (VHL) tumor suppressor protein by components of the VHL ubiquitin ligase. J Biol Chem. 2002;277:30388-93 pubmed
    The multiprotein von Hippel-Lindau (VHL) tumor suppressor (CBC(VHL), Cul2-Elongin BC-VHL) and SCF (Skp1-Cul1/Cdc53-F-box protein) complexes are members of structurally related families of E3 ubiquitin ligases that use a heterodimeric ..
  16. 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
    ..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)...
  17. Hansen W, Ohh M, Moslehi J, Kondo K, Kaelin W, Welch W. Diverse effects of mutations in exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity. Mol Cell Biol. 2002;22:1947-60 pubmed
    ..containing TCP-1 (CCT or TRiC) en route to assembly with elongin B/C and the subsequent formation of the VCB-Cul2 ubiquitin ligase...
  18. Chua Y, Boh B, Ponyeam W, Hagen T. Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo. PLoS ONE. 2011;6:e16071 pubmed publisher
    ..In conclusion, our study suggests that CAND1 does not function by sequestering cullins in vivo to prevent substrate receptor autoubiquitination and is likely to regulate cullin RING ligase activity via alternative mechanisms. ..
  19. 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. ..
  20. 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...
  21. 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
    ..Hence, Hs-cul-2 may be required for VHL function and, therefore, may be a candidate human tumor-suppressor gene. ..
  22. Ghanem A, Schweitzer K, Naumann M. Catalytic domain of deubiquitinylase USP48 directs interaction with Rel homology domain of nuclear factor kappaB transcription factor RelA. Mol Biol Rep. 2019;46:1369-1375 pubmed publisher
    ..mechanisms which comprise ubiquitinylation by a multimeric ubiquitin ligase containing Elongins B and C, cullin-2 (Cul2) and suppressor of cytokine signaling 1 (SOCS1), but also USP48-dependent deubiquitinylation...
  23. Hu J, McCall C, Ohta T, Xiong Y. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol. 2004;6:1003-9 pubmed, and binds to an amino-terminal region in CUL4A in a manner analogous to SKP1, SOCS and BTB binding to CUL1, CUL2 and CUL3, respectively...
  24. Qian Y, Ng C, Schulz C. CSN maintains the germline cellular microenvironment and controls the level of stem cell genes via distinct CRLs in testes of Drosophila melanogaster. Dev Biol. 2015;398:68-79 pubmed publisher
    ..Reducing cullin2 (cul2) from the somatic support cells disrupted germline enclosure, while reducing cullin1 (cul1) from the somatic ..
  25. Uchida T, Tamaki Y, Ayaki T, Shodai A, Kaji S, Morimura T, et al. CUL2-mediated clearance of misfolded TDP-43 is paradoxically affected by VHL in oligodendrocytes in ALS. Sci Rep. 2016;6:19118 pubmed publisher
    ..Here we identified a cullin-2 (CUL2) RING complex as a novel ubiquitin ligase for fragmented forms of TDP-43...
  26. Zhang W, Wang H, Li Z, Liu X, Liu G, Harris R, et al. Cellular requirements for bovine immunodeficiency virus Vif-mediated inactivation of bovine APOBEC3 proteins. J Virol. 2014;88:12528-40 pubmed publisher
    ..In this study, we show that BIV Vif interacts with Cullin 2 (CUL2), ELOB/C, and RBX1, but not with CBF-β or CUL5, to form a CRL2 E3 ubiquitin ligase and degrade the ..
  27. Yun J, Kim Y, Tomida A, Choi C. Regulation of DNA topoisomerase IIalpha stability by the ECV ubiquitin ligase complex. Biochem Biophys Res Commun. 2009;389:5-9 pubmed publisher
    ..and VHL were ectopically expressed in HT1080 and HEK293T cells, topo IIalpha was degraded most prominently in cullin 2- and VHL-expressing cells...
  28. Fulcher L, Hutchinson L, MacArtney T, Turnbull C, Sapkota G. Targeting endogenous proteins for degradation through the affinity-directed protein missile system. Open Biol. 2017;7: pubmed publisher
    ..missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to ..
  29. Lee Y, Lim B, Lee S, Lee W, Kim Y, Kim M, et al. ANKRD9 is associated with tumor suppression as a substrate receptor subunit of ubiquitin ligase. Biochim Biophys Acta Mol Basis Dis. 2018;1864:3145-3153 pubmed publisher
    ..ANKRD9 associates with CUL5 (not CUL2), ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin-RING superfamily E3 ligase ..
  30. Yamaki Y, Kagawa H, Hatta T, Natsume T, Kawahara H. The C-terminal cytoplasmic tail of hedgehog receptor Patched1 is a platform for E3 ubiquitin ligase complexes. Mol Cell Biochem. 2016;414:1-12 pubmed publisher
    ..In particular, Ptc1 ICD7 interacted with most components of the Cullin-2 (CUL2)-based E3 ligase complex, including TCEB1 (EloC), TCEB2 (EloB), ZYG11B, and CUL2 itself...
  31. Okagaki R, Haaning A, Bilgic H, Heinen S, Druka A, Bayer M, et al. ELIGULUM-A Regulates Lateral Branch and Leaf Development in Barley. Plant Physiol. 2018;176:2750-2760 pubmed publisher
    ..The barley (Hordeum vulgare) uniculm2 (cul2) mutation blocks axillary meristem development, and mutant plants lack lateral branches (tillers) that normally ..
  32. Guo Y, Dong L, Qiu X, Wang Y, Zhang B, Liu H, et al. Structural basis for hijacking CBF-? and CUL5 E3 ligase complex by HIV-1 Vif. Nature. 2014;505:229-33 pubmed publisher
    ..Together, our data reveal the structural basis for Vif hijacking of the CBF-? and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs. ..
  33. Su X, Wang H, Zhou X, Li Z, Zheng B, Zhang W. Jembrana disease virus Vif antagonizes the inhibition of bovine APOBEC3 proteins through ubiquitin-mediate protein degradation. Virology. 2018;519:53-63 pubmed publisher
    ..In this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2 and RBX1 but without the need of CBF-? to form E3 ubiquitin ligase and induces the degradation of btA3 proteins...
  34. Mousnier A, Kubat N, Massias Simon A, Segeral E, Rain J, Benarous R, et al. von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step. Proc Natl Acad Sci U S A. 2007;104:13615-20 pubmed
    ..chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase...
  35. Xu J, Li L, Yu G, Ying W, Gao Q, Zhang W, et al. The neddylation-cullin 2-RBX1 E3 ligase axis targets tumor suppressor RhoB for degradation in liver cancer. Mol Cell Proteomics. 2015;14:499-509 pubmed publisher
    ..Specifically, cullin 2-RBX1 E3 ligase, which requires NEDD8 conjugation for its activation, interacted with RhoB and promoted its ..
  36. Kim T, Jackson S, Xiong Y, Whitsett T, Lobello J, Weiss G, et al. CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth. Proc Natl Acad Sci U S A. 2013;110:16868-73 pubmed publisher
    ..In summary, we identify a posttranslational mechanism for loss of DLC1 and a linkage between CRL4A-FBXW5-associated oncogenesis and regulation of RhoA signaling. ..
  37. Kazemi Z, Rudbari H, Sahihi M, Mirkhani V, Moghadam M, Tangestaninejad S, et al. Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study. J Photochem Photobiol B. 2016;162:448-462 pubmed publisher
    Novel metal-based drug candidate including VOL2, NiL2, CuL2 and PdL2 have been synthesized from 2-hydroxy-1-allyliminomethyl-naphthalen ligand and have been characterized by means of elemental analysis (CHN), FT-IR and UV-vis ..
  38. Annaraj B, Neelakantan M. Synthesis, crystal structure, spectral characterization and biological exploration of water soluble Cu(II) complexes of vitamin B6 derivative. Eur J Med Chem. 2015;102:1-8 pubmed publisher
    ..of Copper(II) complexes of a Schiff base derived from vitamin B6 component (pyridoxal) and ethanol amine [CuL2] (1), and its mixed ligand complexes [Cu(L)(N,N')]NO3, where N,N' is bipyridine (2) and 1,10-phenanthroline (3) are ..
  39. Yasukawa T, Kamura T, Kitajima S, Conaway R, Conaway J, Aso T. Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1. EMBO J. 2008;27:3256-66 pubmed publisher
    ..Taken together, our results suggest that mammalian Elongin A is directly involved in ubiquitylation and degradation of Rpb1 following DNA damage. ..
  40. Heir P, Ohh M. Hydroxylation-Dependent Interaction of Substrates to the Von Hippel-Lindau Tumor Suppressor Protein (VHL). Methods Mol Biol. 2016;1458:87-94 pubmed publisher
    ..von Hippel-Lindau Tumor Suppressor protein (VHL) containing E3-ubiquitin ligase complex known as ECV (Elongins B/C, CUL2, VHL)...
  41. Cardote T, Gadd M, Ciulli A. Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex. Structure. 2017;25:901-911.e3 pubmed publisher
    ..Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL...
  42. Chen P, Yao G. The role of cullin proteins in gastric cancer. Tumour Biol. 2016;37:29-37 pubmed publisher
    ..There are seven cullin proteins that have been identified in eukaryotes: CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, and CUL7/p53-associated parkin-like cytoplasmic protein...
  43. Bommelje C, Weeda V, Huang G, Shah K, Bains S, Buss E, et al. Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity and nuclear localization. Clin Cancer Res. 2014;20:372-81 pubmed publisher
    ..Our data suggest that SCCRO5 has oncogenic potential that requires its function as a component of the neddylation E3. Neddylation activity and nuclear localization of SCCRO5 are important for its in vivo function. ..
  44. Essers P, Klasson T, Pereboom T, Mans D, Nicastro M, Boldt K, et al. The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2. Oncogene. 2015;34:771-9 pubmed publisher
    ..Taken together, our study describes a new mechanism for p53 stabilization through PDCD5 upon hypoxia or pVHL loss, and reveals new clinical potential for the treatment of pathobiological disorders linked to hypoxic stress. ..
  45. Wadelin F, Fulton J, Collins H, Tertipis N, Bottley A, Spriggs K, et al. PRAME is a golgi-targeted protein that associates with the Elongin BC complex and is upregulated by interferon-gamma and bacterial PAMPs. PLoS ONE. 2013;8:e58052 pubmed publisher
  46. Russell R, Sufan R, Zhou B, Heir P, Bunda S, Sybingco S, et al. Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia. Nat Med. 2011;17:845-53 pubmed publisher
    ..These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia. ..
  47. Mao X, Gluck N, Chen B, Starokadomskyy P, Li H, Maine G, et al. COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding. J Biol Chem. 2011;286:32355-65 pubmed publisher
    ..We show that COMMD1 interacts with multiple Cullins, that the COMMD1-Cul2 complex cannot bind CAND1, and that, conversely, COMMD1 can actively displace CAND1 from CRLs...
  48. Sun W, Kato H, Kitajima S, Lee K, Gradin K, Okamoto T, et al. Interaction between von Hippel-Lindau Protein and Fatty Acid Synthase Modulates Hypoxia Target Gene Expression. Sci Rep. 2017;7:7190 pubmed publisher
    ..Therefore, pVHL-FASN interaction plays a regulatory role for HIFs and their target gene expression. ..
  49. Iwai K, Yamanaka K, Kamura T, Minato N, Conaway R, Conaway J, et al. Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A. 1999;96:12436-41 pubmed
    ..This is also, to our knowledge, the first example of a human tumor-suppressor protein being directly involved in the ubiquitin conjugation system which leads to the targeted degradation of substrate proteins. ..
  50. Foxler D, Bridge K, James V, Webb T, Mee M, Wong S, et al. The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity. Nat Cell Biol. 2012;14:201-8 pubmed publisher
    ..LIMD1 family member proteins Ajuba and WTIP also bind to VHL and PHDs 1 and 3, indicating that these LIM domain-containing proteins represent a previously unrecognized group of hypoxic regulators. ..
  51. Ietta F, Wu Y, Winter J, Xu J, Wang J, Post M, et al. Dynamic HIF1A regulation during human placental development. Biol Reprod. 2006;75:112-21 pubmed
    ..At the same time the association of VHL and Cullin 2 as well as ubiquitination of HIF1A was maximal...
  52. Sufan R, Moriyama E, Mariampillai A, Roche O, Evans A, Alajez N, et al. Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour suppressor complex. EMBO Mol Med. 2009;1:66-78 pubmed publisher
    ..These findings introduce the concept and feasibility of 'bio-tailored' enzymes in the treatment of HIF-overexpressing tumours. ..
  53. Choo Y, Boh B, Lou J, Eng J, Leck Y, Anders B, et al. Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity. Mol Biol Cell. 2011;22:4706-15 pubmed publisher
    ..The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle. ..
  54. Furukawa M, Ohta T, Xiong Y. Activation of UBC5 ubiquitin-conjugating enzyme by the RING finger of ROC1 and assembly of active ubiquitin ligases by all cullins. J Biol Chem. 2002;277:15758-65 pubmed
    ..We suggest that RING-E2, rather than cullin-RING, constitutes the catalytic core of the ubiquitin ligase and that one major function of the cullin subunit is to assemble the RING-E2 catalytic core and substrates together. ..
  55. Menon S, Tsuge T, Dohmae N, Takio K, Wei N. Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome. BMC Biochem. 2008;9:1 pubmed publisher
    ..It forms tertiary complexes with fully assembled CRL E3 complexes such as SCFSkp2, Elongin B/C -Cul2- VHL and Cul4-DDB complex by binding to both N-terminal and C-terminal domain of cullins...
  56. 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. ..
  57. Curtis V, Ehrentraut S, Campbell E, Glover L, Bayless A, Kelly C, et al. Stabilization of HIF through inhibition of Cullin-2 neddylation is protective in mucosal inflammatory responses. FASEB J. 2015;29:208-15 pubmed publisher
    ..Pharmacologic inhibition of cullin neddylation may provide a therapeutic opportunity in mucosal inflammatory disease. ..
  58. 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. ..
  59. 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. ..
  60. Ohta T, Michel J, Schottelius A, Xiong Y. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell. 1999;3:535-41 pubmed
    ..Ubiquitination of phosphorylated I kappa B alpha can be catalyzed by the ROC1 immunocomplex in vitro. Hence, combinations of ROC/APC11 and cullin proteins proteins potentially constitute a wide variety of ubiquitin ligases. ..
  61. Cordero Espinoza L, Hagen T. Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130). Biol Open. 2013;2:838-44 pubmed publisher
    ..could extend to other CRLs; however, overexpression of SAP130 is unable to affect the protein stability of the Cul2 and Cul3 substrates, HIF-1 and NRF-2...
  62. Kuchay S, Duan S, Schenkein E, Peschiaroli A, Saraf A, Florens L, et al. FBXL2- and PTPL1-mediated degradation of p110-free p85? regulatory subunit controls the PI(3)K signalling cascade. Nat Cell Biol. 2013;15:472-80 pubmed publisher
    ..We propose that FBXL2 and PTPL1 suppress p85? levels, preventing the inhibition of PI(3)K by an excess of free p85 that could compete with p85-p110 heterodimers for IRS1. ..
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