CUL4A

Summary

Gene Symbol: CUL4A
Description: cullin 4A
Alias: cullin-4A, CUL-4A
Species: human
Products:     CUL4A

Top Publications

  1. Bondar T, Kalinina A, Khair L, Kopanja D, Nag A, Bagchi S, et al. Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Mol Cell Biol. 2006;26:2531-9 pubmed
    DDB1, a subunit of the damaged-DNA binding protein DDB, has been shown to function also as an adaptor for Cul4A, a member of the cullin family of E3 ubiquitin ligase...
  2. Nag A, Bagchi S, Raychaudhuri P. Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Cancer Res. 2004;64:8152-5 pubmed
    The cullin 4A (Cul4A) gene is amplified and overexpressed in breast and hepatocellular carcinomas...
  3. Yan Y, Zhang X, Legerski R. Artemis interacts with the Cul4A-DDB1DDB2 ubiquitin E3 ligase and regulates degradation of the CDK inhibitor p27. Cell Cycle. 2011;10:4098-109 pubmed publisher
    ..We show here that Artemis interacts with the Cul4A-DDB1 E3 ubiquitin ligase via a direct interaction with the substrate-specificity receptor DDB2...
  4. Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A. CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell. 2010;40:9-21 pubmed publisher
    ..These results demonstrate a central role of CRL4(Cdt2)-dependent cell-cycle regulation of Set8 for the maintenance of a stable epigenetic state essential for cell viability. ..
  5. Kipreos E, Lander L, Wing J, He W, Hedgecock E. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell. 1996;85:829-39 pubmed
    ..cul-1 represents a conserved family of genes, designated cullins, with at least five members in nematodes, six in humans, and three in budding yeast. ..
  6. Yang Y, Hung M, Wang Y, Ni J, Mao J, Hsieh D, et al. Lung tumourigenesis in a conditional Cul4A transgenic mouse model. J Pathol. 2014;233:113-23 pubmed publisher
    Cullin4A (Cul4A) is a scaffold protein that assembles cullin-RING ubiquitin ligase (E3) complexes and regulates many cellular events, including cell survival, development, growth and cell cycle control...
  7. Terai K, Abbas T, Jazaeri A, Dutta A. CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Mol Cell. 2010;37:143-9 pubmed publisher
    ..We propose that CRL4(Cdt2) regulates PCNA-dependent TLS associated with stresses accompanying DNA replication. ..
  8. Kotake Y, Zeng Y, Xiong Y. DDB1-CUL4 and MLL1 mediate oncogene-induced p16INK4a activation. Cancer Res. 2009;69:1809-14 pubmed publisher
    ..We showed that CUL4A directly binds to p16 and that silencing DDB1 blocks Ras-induced p16 activation...
  9. Casey L, Wen X, de Noronha C. The functions of the HIV1 protein Vpr and its action through the DCAF1.DDB1.Cullin4 ubiquitin ligase. Cytokine. 2010;51:1-9 pubmed publisher
    ..Here, we discuss the multiple functions that have been linked to Vpr expression and summarize the current knowledge on the role of the ubiquitin ligase complex in carrying out a subset of these activities. ..

More Information

Publications87

  1. Srivastava S, Swanson S, Manel N, Florens L, Washburn M, Skowronski J. Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog. 2008;4:e1000059 pubmed publisher
  2. Higa L, Mihaylov I, Banks D, Zheng J, Zhang H. Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol. 2003;5:1008-15 pubmed
    ..Our study reveals an evolutionarily conserved and uncharacterized G1 checkpoint that induces CDT1 proteolysis by the CUL4-ROC1 ubiquitin E3 ligase and CSN complexes in response to DNA damage. ..
  3. Le Rouzic E, Morel M, Ayinde D, Belaïdouni N, Letienne J, Transy C, et al. Assembly with the Cul4A-DDB1DCAF1 ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation. J Biol Chem. 2008;283:21686-92 pubmed publisher
    ..immunodeficiency virus type 1 Vpr protein, which promotes cell cycle arrest by recruiting the DCAF1 adaptor of the Cul4A-DDB1 ubiquitin ligase, a finding now confirmed by several groups...
  4. Huh J, Piwnica Worms H. CRL4(CDT2) targets CHK1 for PCNA-independent destruction. Mol Cell Biol. 2013;33:213-26 pubmed publisher
    ..Although both CRL1 and CRL4 ubiquitinate CHK1, we report that they bind CHK1 in distinct cellular compartments. Our study provides insight into how elevated CDT2 expression levels may provide tumors with a proliferative advantage. ..
  5. Scrima A, Fischer E, Lingaraju G, Böhm K, Cavadini S, Thoma N. Detecting UV-lesions in the genome: The modular CRL4 ubiquitin ligase does it best!. FEBS Lett. 2011;585:2818-25 pubmed publisher
    ..We will examine the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 focusing on shared architectural, targeting and regulatory principles. ..
  6. Leung Pineda V, Huh J, Piwnica Worms H. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Res. 2009;69:2630-7 pubmed publisher
    ..DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B. We report that Cul4A/DDB1 negatively regulates Chk1 stability in vivo...
  7. Nag A, Bondar T, Shiv S, Raychaudhuri P. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Mol Cell Biol. 2001;21:6738-47 pubmed
    ..Studies presented here identify a specific function of the Cul-4A gene, which is amplified and overexpressed in breast cancers. ..
  8. Huang C, Chiang S, Lin T, Chiou S, Chow K. HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS ONE. 2012;7:e33657 pubmed publisher
    ..in membrane potential (MMP) by posttranscriptionally reducing the expression of mitofusin 2 (Mfn2) via VprBP-DDB1-CUL4A ubiquitin ligase complex, gradually weakening MOM, and increasing mitochondrial deformation...
  9. Schröfelbauer B, Hakata Y, Landau N. HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proc Natl Acad Sci U S A. 2007;104:4130-5 pubmed
    ..The interaction with DDB1 may explain several of the diverse biological functions of Vpr and suggests potential roles for Vpr in HIV-1 replication. ..
  10. Chew E, Poobalasingam T, Hawkey C, Hagen T. Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells--evidence for cullin dimerization. Cell Signal. 2007;19:1071-80 pubmed
    ..Cul3, but not Cul1 homooligomerization is dependent on substrate recognition subunit dimer formation. As shown for other E3 ubiquitin ligases, dimerization may play a role in regulating the activity of cullin-based E3 ligases. ..
  11. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345-50 pubmed publisher
    ..CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks...
  12. 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. ..
  13. Zhang Y, Morrone G, Zhang J, Chen X, Lu X, Ma L, et al. CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein. EMBO J. 2003;22:6057-67 pubmed
    ..These results revealed a novel regulatory mechanism of hematopoiesis by ubiquitin-dependent proteolysis. ..
  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. 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. ..
  16. Belzile J, Duisit G, Rougeau N, Mercier J, Finzi A, Cohen E. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog. 2007;3:e85 pubmed
    ..We found that damaged DNA binding protein 1 (DDB1), viral protein R binding protein (VPRBP), and cullin 4A (CUL4A)--components of a CUL4A E3 ubiquitin ligase complex, DDB1-CUL4A(VPRBP)--were able to associate with Vpr...
  17. Han J, Zhang H, Zhang H, Wang Z, Zhou H, Zhang Z. A Cul4 E3 ubiquitin ligase regulates histone hand-off during nucleosome assembly. Cell. 2013;155:817-29 pubmed publisher
    ..Similar phenotypes occur in human cells in which the ortholog of Rtt101(Mms1), Cul4A(DDB1), is depleted...
  18. 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. ..
  19. Melchor L, Saucedo Cuevas L, Muñoz Repeto I, Rodriguez Pinilla S, Honrado E, Campoverde A, et al. Comprehensive characterization of the DNA amplification at 13q34 in human breast cancer reveals TFDP1 and CUL4A as likely candidate target genes. Breast Cancer Res. 2009;11:R86 pubmed publisher
    ..Protein expression levels of two of these genes (TFDP1 and CUL4A) were assessed by immunohistochemical assays on the same tissue microarrays used for FISH studies, and correlated ..
  20. Li B, Jia N, Kapur R, Chun K. Cul4A targets p27 for degradation and regulates proliferation, cell cycle exit, and differentiation during erythropoiesis. Blood. 2006;107:4291-9 pubmed
    ..b>Cul4A encodes a core subunit of a ubiquitin ligase that targets proteins for ubiquitin-mediated degradation, and Cul4A-..
  21. Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, et al. A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998;12:2263-8 pubmed
  22. Wang H, Zhai L, Xu J, Joo H, Jackson S, Erdjument Bromage H, et al. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006;22:383-94 pubmed
    ..Reduction of histone H3 and H4 ubiquitylation by knockdown of CUL4A impairs recruitment of the repair protein XPC to the damaged foci and inhibits the repair process...
  23. El Mahdy M, Zhu Q, Wang Q, Wani G, Praetorius Ibba M, Wani A. Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC. J Biol Chem. 2006;281:13404-11 pubmed
    ..Here, we have provided evidence that Cullin 4A (CUL-4A), a key component of CUL-4A-based ubiquitin ligase, mediates DDB2 degradation at the damage sites and ..
  24. Liu L, Lee S, Zhang J, Peters S, Hannah J, Zhang Y, et al. CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis. Mol Cell. 2009;34:451-60 pubmed publisher
    ..Here we demonstrate that the CUL4A ubiquitin ligase restricts the cellular repair capacity by orchestrating the concerted actions of nucleotide ..
  25. 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
    ..We determined that DLC1 was ubiquitinated and degraded by cullin 4A-RING ubiquitin ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor...
  26. Zhang Y, Otterness D, Chiang G, Xie W, Liu Y, Mercurio F, et al. Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway. Mol Cell. 2005;19:607-18 pubmed
    ..The ubiquitination of Chk1 is mediated by E3 ligase complexes containing Cul1 or Cul4A. Treatment of cells with the anticancer agent camptothecin (CPT) triggers Chk1 destruction, which blocks recovery ..
  27. Schröfelbauer B, Yu Q, Zeitlin S, Landau N. Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases. J Virol. 2005;79:10978-87 pubmed
    ..The findings highlight the importance of cytidine deamination in the virus replication cycle and present a novel function for Vpr. ..
  28. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev. 2008;22:2496-506 pubmed publisher
    ..Finally, we show that the CRL4(Cdt2) and the SCF(Skp2) ubiquitin ligases are redundant with each other in promoting the degradation of p21 during an unperturbed S phase of the cell cycle. ..
  29. Ward J, Davis Z, DeHart J, Zimmerman E, Bosque A, Brunetta E, et al. HIV-1 Vpr triggers natural killer cell-mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLoS Pathog. 2009;5:e1000613 pubmed publisher
    ..ULBP-2 on HIV-1 infected cells is dependent on the ability of Vpr to associate with a protein complex know as Cullin 4a (Cul4a)/damaged DNA binding protein 1 (DDB1) and Cul4a-associated factor-1(DCAF-1) E3 ubiquitin ligase (Cul4a(..
  30. Hu J, Zacharek S, He Y, Lee H, Shumway S, Duronio R, et al. WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Dev. 2008;22:866-71 pubmed publisher
    ..Overexpression of FBW5 or CUL4A promotes TSC2 protein degradation, and this is abrogated by the coexpression of TSC1...
  31. Huang J, Chen J. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene. 2008;27:4056-64 pubmed publisher
    ..Together, our data revealed a novel regulatory mechanism for the tumor suppressor function of Merlin. ..
  32. Senga T, Sivaprasad U, Zhu W, Park J, Arias E, Walter J, et al. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J Biol Chem. 2006;281:6246-52 pubmed
    ..Therefore PCNA, the matchmaker for many proteins involved in DNA and chromatin metabolism, also serves to promote the targeted degradation of associated proteins in S-phase or after DNA damage. ..
  33. Miranda Carboni G, Krum S, Yee K, Nava M, Deng Q, Pervin S, et al. A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. Genes Dev. 2008;22:3121-34 pubmed publisher
    ..Instead, turnover required Cullin 4A and Cullin 4B, components of an alternative E3 ubiquitin ligase induced in response to active Wnt signaling...
  34. Yasui K, Arii S, Zhao C, Imoto I, Ueda M, Nagai H, et al. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Hepatology. 2002;35:1476-84 pubmed
    ..3 of those genes, TFDP1, CUL4A (cullin 4A), and CDC16 (cell division cycle 16), showed distinct amplification and consequent over-expression in some cell ..
  35. Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, et al. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003;113:357-67 pubmed
    ..Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity...
  36. Pick E, Lau O, Tsuge T, Menon S, Tong Y, Dohmae N, et al. Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes. Mol Cell Biol. 2007;27:4708-19 pubmed
    ..Human DET1 has recently been isolated as one of the DDB1- and Cul4A-associated factors, along with an array of WD40-containing substrate receptors of the Cul4A-DDB1 ubiquitin ligase...
  37. Casey Klockow L, Sharifi H, Wen X, Flagg M, Furuya A, Nekorchuk M, et al. The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection. Virology. 2013;444:191-202 pubmed publisher
    ..Our results support a model in which Vpr complexes with human Dicer to boost its interaction with the CRL4(DCAF1) ubiquitin ligase complex and its subsequent degradation. ..
  38. Li W, You L, Cooper J, Schiavon G, Pepe Caprio A, Zhou L, et al. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell. 2010;140:477-90 pubmed publisher
    ..We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1). ..
  39. Wang Y, Wen M, Kwon Y, Xu Y, Liu Y, Zhang P, et al. CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression. Cancer Res. 2014;74:520-31 pubmed publisher
    The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated...
  40. Liu J, Furukawa M, Matsumoto T, Xiong Y. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol Cell. 2002;10:1511-8 pubmed
    ..We suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes. ..
  41. Sung C, Dahl J, Yim H, Rodig S, Benjamin T. Transcriptional and post-translational regulation of the quiescence factor and putative tumor suppressor p150(Sal2). FASEB J. 2011;25:1275-83 pubmed publisher
    ..A CUL4/DDB1 E3 ligase containing RBBP7 as the p150(Sal2) receptor has been identified as mediating the destruction of p150(Sal2) as cells transition from a quiescent to an actively growing state. ..
  42. Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T. CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem. 2008;283:29045-52 pubmed publisher
    ..p21 was co-immunoprecipitated with Cul4A and DDB1 proteins when expressed in cells. The purified Cul4A-DDB1(Cdt2) complex ubiquitinated p21 in vitro...
  43. Hu J, Xiong Y. An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. J Biol Chem. 2006;281:3753-6 pubmed
  44. Higa L, Yang X, Zheng J, Banks D, Wu M, Ghosh P, et al. Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation. Cell Cycle. 2006;5:71-7 pubmed
    ..Coelimination of Dacapo with CUL4 abolishes the G(1) cell cycle arrest. In human cells, inactivation of CUL4A induces CDK inhibitor p27(Kip1) stabilization and G(1) cell cycle arrest which is dependent on the presence of p27,..
  45. McCall C, Miliani de Marval P, Chastain P, Jackson S, He Y, Kotake Y, et al. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol. 2008;28:5621-33 pubmed publisher
    ..We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of the COP9/signalsome, and DDA1...
  46. Katiyar S, Liu E, Knutzen C, Lang E, Lombardo C, Sankar S, et al. REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO Rep. 2009;10:866-72 pubmed publisher
    ..Here, we show that REDD1 is subject to ubiquitin-mediated degradation mediated by the CUL4A-DDB1-ROC1-beta-TRCP E3 ligase complex and through the activity of glycogen synthase kinase 3beta...
  47. Jiang L, Rong R, Sheikh M, Huang Y. Cullin-4A·DNA damage-binding protein 1 E3 ligase complex targets tumor suppressor RASSF1A for degradation during mitosis. J Biol Chem. 2011;286:6971-8 pubmed publisher
    ..In the present study, we have identified Cullin-4A (CUL4A) as a novel E3 ligase for RASSF1A...
  48. Ahn J, Vu T, Novince Z, Guerrero Santoro J, Rapic Otrin V, Gronenborn A. HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a substrate recognition subunit of a cullin 4A-ring E3 ubiquitin ligase for proteasome-dependent degradation. J Biol Chem. 2010;285:37333-41 pubmed publisher
    ..The ligase is composed of cullin 4A (CUL4A), RING H2 finger protein (RBX1), DNA damage-binding protein 1 (DDB1), and a substrate recognition subunit,..
  49. Ren S, Xu C, Cui Z, Yu Y, Xu W, Wang F, et al. Oncogenic CUL4A determines the response to thalidomide treatment in prostate cancer. J Mol Med (Berl). 2012;90:1121-32 pubmed publisher
    ..Here we demonstrate that CUL4A plays an oncogenic role in prostate cancer development and prostate cancer cells with higher level of CUL4A are ..
  50. Hrecka K, Gierszewska M, Srivastava S, Kozaczkiewicz L, Swanson S, Florens L, et al. Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A. 2007;104:11778-83 pubmed publisher
  51. Kapetanaki M, Guerrero Santoro J, Bisi D, Hsieh C, Rapic Otrin V, Levine A. The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Proc Natl Acad Sci U S A. 2006;103:2588-93 pubmed
    ..The UV-DDB complex is a component of the newly identified cullin 4A-based ubiquitin E3 ligase, DDB1-CUL4A(DDB2)...
  52. Maudet C, Sourisce A, Dragin L, Lahouassa H, Rain J, Bouaziz S, et al. HIV-1 Vpr induces the degradation of ZIP and sZIP, adaptors of the NuRD chromatin remodeling complex, by hijacking DCAF1/VprBP. PLoS ONE. 2013;8:e77320 pubmed publisher
    ..HIV-1 and HIV-2) is thought to inactivate several host proteins through the hijacking of the DCAF1 adaptor of the Cul4A ubiquitin ligase...
  53. 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
    ..The Cul4A gene is amplified in human breast and liver cancers, and loss-of-function of Cul4 results in the accumulation of ..
  54. 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. ..
  55. 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. ..
  56. Lo Y, Ho P, Wang S. Epidermal growth factor receptor protects proliferating cell nuclear antigen from cullin 4A protein-mediated proteolysis. J Biol Chem. 2012;287:27148-57 pubmed publisher
    ..we show that, in the absence of Tyr-211 phosphorylation, PCNA is subject to polyubiquitylation at Lys-164 by the CUL4A E3 ligase, resulting in the degradation of PCNA...
  57. Gastaldello S, Hildebrand S, Faridani O, Callegari S, Palmkvist M, Di Guglielmo C, et al. A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases. Nat Cell Biol. 2010;12:351-61 pubmed publisher
    ..Homologues encoded by other herpesviruses share the deneddylase activity. Thus, these enzymes are likely to have a key function in the virus life cycle by inducing a replication-permissive S-phase-like cellular environment...
  58. Hung M, Mao J, Xu Z, Yang C, Yu J, Harvard C, et al. Cul4A is an oncogene in malignant pleural mesothelioma. J Cell Mol Med. 2011;15:350-8 pubmed publisher
    b>Cullin 4A (Cul4A) is important in cell survival, development, growth and the cell cycle, but its role in mesothelioma has not been studied...
  59. Fischer E, Scrima A, Böhm K, Matsumoto S, Lingaraju G, Faty M, et al. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Cell. 2011;147:1024-39 pubmed publisher
    ..The structures of the fully assembled DDB1-DDB2-CUL4A/B-RBX1 (CRL4(DDB2)) ligases reveal that the mobility of the ligase arm creates a defined ubiquitination zone ..
  60. Higa L, Banks D, Wu M, Kobayashi R, Sun H, Zhang H. L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. Cell Cycle. 2006;5:1675-80 pubmed
    ..Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage. ..
  61. Wertz I, O Rourke K, Zhang Z, Dornan D, Arnott D, Deshaies R, et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science. 2004;303:1371-4 pubmed
    ..factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1...
  62. Choi S, Wright J, Gerber S, Cole M. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. Genes Dev. 2010;24:1236-41 pubmed publisher
    ..These studies identify a novel pathway targeting Myc degradation that is suppressed in cancer cells. ..
  63. Wen X, Duus K, Friedrich T, de Noronha C. The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. J Biol Chem. 2007;282:27046-57 pubmed
    ..Vpr, thus, functions like the HIV1 proteins Vif and Vpu to usurp cellular ubiquitin ligases for viral functions. ..
  64. Sansam C, Shepard J, Lai K, Ianari A, Danielian P, Amsterdam A, et al. DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint. Genes Dev. 2006;20:3117-29 pubmed
    ..First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint. ..
  65. Sharma P, Nag A. CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases. Open Biol. 2014;4:130217 pubmed publisher
    The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins...
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    ..Importantly, human cancers harboring mutations in Fbx4, the cyclin D1 E3 ligase, exhibit nuclear cyclin D1 accumulation and increased PRMT5 activity. ..
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    ..The enhanced expression of all Cul-family proteins except Cul-5 was observed in a variety of tumor cell lines. ..
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    ..This in turn suggests that both proteins have evolved to preserve interaction with the same Cul4 ubiquitin ligase while diverging in the recognition of host substrates targeted for proteasomal degradation. ..
  69. Olma M, Roy M, Le Bihan T, Sumara I, Maerki S, Larsen B, et al. An interaction network of the mammalian COP9 signalosome identifies Dda1 as a core subunit of multiple Cul4-based E3 ligases. J Cell Sci. 2009;122:1035-44 pubmed publisher
    ..Cells depleted of Dda1 spontaneously accumulated double-stranded DNA breaks in a similar way to Cul4A-, Cul4B- or Wdr23-depleted cells, indicating that Dda1 interacts physically and functionally with CRL4 complexes...
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    b>CUL4A and B encode subunits of E3-ubiquitin ligases implicated in diverse processes including nucleotide excision repair, regulating gene expression and controlling DNA replication fork licensing...
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    ..On the other hand, Vpr-induced G2 arrest was impaired when the intracellular level of DDB1 or Cullin 4A was reduced by siRNA treatment...
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    ..These results suggest that up-regulation of cul-4A may play an important role in tumor progression. ..
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    ..from the re-replication preventing activity, we identified a non-canonical Cullin-4(CDT2) complex, containing both CUL4A and CUL4B, associated to the COP9 signalosome, that controls a RAD18-dependent damage avoidance pathway essential ..
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    ..Together, our studies reveal a common yet promiscuous structural element that is important for the assembly of cellular and virally hijacked CUL4-DDB1 E3 complexes. ..
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    ..Many CRL4 complexes are involved in chromatin regulation and are frequently hijacked by different viruses. ..
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    ..Inactivation of CUL4A, L2DTL, PCNA, DDB1 or ROC1 induced p53 stabilization and growth arrest...