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A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.

Li T, Robert EI, van Breugel PC, Strubin M, Zheng N
Nat Struct Mol Biol 17 105-11 (2010)
Related entries: 3i7h, 3i7k, 3i7l, 3i7n, 3i7o, 3i7p, 3i89, 3i8c

Cited: 129 times
EuropePMC logo PMID: 19966799

Abstract

The cullin 4-DNA-damage-binding protein 1 (CUL4-DDB1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. Here we report the crystal structure of DDB1 in complex with a central fragment of hepatitis B virus X protein (HBx), whose DDB1-binding activity is important for viral infection. The structure reveals that HBx binds DDB1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus SV5-V protein despite their sequence divergence. Our structure-based functional analysis suggests that, like SV5-V, HBx captures DDB1 to redirect the ubiquitin ligase activity of the CUL4-DDB1 E3 ligase. We also identify the alpha-helical motif shared by these viral proteins in the cellular substrate-recruiting subunits of the E3 complex, the DDB1-CUL4-associated factors (DCAFs) that are functionally mimicked by the viral hijackers. 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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  2. Modeling the CRL4A ligase complex to predict target protein ubiquitination induced by cereblon-recruiting PROTACs. Bai N, Riching KM, Makaju A, Wu H, Acker TM, Ou SC, Zhang Y, Shen X, Bulloch DN, Rui H, Gibson BW, Daniels DL, Urh M, Rock BM, Humphreys SC. J Biol Chem 298 101653 (2022)


Reviews citing this publication (45)

  1. Ubiquitin Ligases: Structure, Function, and Regulation. Zheng N, Shabek N. Annu Rev Biochem 86 129-157 (2017)
  2. Molecular biology of hepatitis B virus infection. Seeger C, Mason WS. Virology 479-480 672-686 (2015)
  3. The photomorphogenic repressors COP1 and DET1: 20 years later. Lau OS, Deng XW. Trends Plant Sci 17 584-593 (2012)
  4. Structure and function of WD40 domain proteins. Xu C, Min J. Protein Cell 2 202-214 (2011)
  5. Protein neddylation: beyond cullin-RING ligases. Enchev RI, Schulman BA, Peter M. Nat Rev Mol Cell Biol 16 30-44 (2015)
  6. Viral hepatitis and liver cancer. Ringelhan M, McKeating JA, McKeating JA, Protzer U. Philos Trans R Soc Lond B Biol Sci 372 20160274 (2017)
  7. Hepatitis B virus X gene and hepatocarcinogenesis. Ng SA, Lee C. J Gastroenterol 46 974-990 (2011)
  8. DNA viruses and the cellular DNA-damage response. Turnell AS, Grand RJ. J Gen Virol 93 2076-2097 (2012)
  9. Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation. Bulatov E, Ciulli A. Biochem J 467 365-386 (2015)
  10. Advancing targeted protein degradation for cancer therapy. Dale B, Cheng M, Park KS, Kaniskan HÜ, Xiong Y, Jin J. Nat Rev Cancer 21 638-654 (2021)
  11. Molecular insights into NF2/Merlin tumor suppressor function. Cooper J, Giancotti FG. FEBS Lett 588 2743-2752 (2014)
  12. Antiviral therapies and prospects for a cure of chronic hepatitis B. Zoulim F, Durantel D. Cold Spring Harb Perspect Med 5 a021501 (2015)
  13. Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B. Hannah J, Zhou P. Gene 573 33-45 (2015)
  14. Hepatitis B Virus X and Regulation of Viral Gene Expression. Slagle BL, Bouchard MJ. Cold Spring Harb Perspect Med 6 a021402 (2016)
  15. A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation-and Beyond? Schreiner S, Nassal M. Viruses 9 E125 (2017)
  16. CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases. Sharma P, Nag A. Open Biol 4 130217 (2014)
  17. Role of HBx in hepatitis B virus persistence and its therapeutic implications. Slagle BL, Bouchard MJ. Curr Opin Virol 30 32-38 (2018)
  18. Lentivirus Vpr and Vpx accessory proteins usurp the cullin4-DDB1 (DCAF1) E3 ubiquitin ligase. Romani B, Cohen EA. Curr Opin Virol 2 755-763 (2012)
  19. Detecting UV-lesions in the genome: The modular CRL4 ubiquitin ligase does it best! Scrima A, Fischer ES, Lingaraju GM, Böhm K, Cavadini S, Thomä NH. FEBS Lett 585 2818-2825 (2011)
  20. Hepatitis B virus HBx protein interactions with the ubiquitin proteasome system. Minor MM, Slagle BL. Viruses 6 4683-4702 (2014)
  21. Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6. Livingston CM, Ramakrishnan D, Strubin M, Fletcher SP, Beran RK. Viruses 9 E69 (2017)
  22. VprBP (DCAF1): a promiscuous substrate recognition subunit that incorporates into both RING-family CRL4 and HECT-family EDD/UBR5 E3 ubiquitin ligases. Nakagawa T, Mondal K, Swanson PC. BMC Mol Biol 14 22 (2013)
  23. Cullin-RING E3 Ubiquitin Ligases: Bridges to Destruction. Nguyen HC, Wang W, Xiong Y. Subcell Biochem 83 323-347 (2017)
  24. Changing the ubiquitin landscape during viral manipulation of the DNA damage response. Weitzman MD, Lilley CE, Chaurushiya MS. FEBS Lett 585 2897-2906 (2011)
  25. Using proteomics to identify the HBx interactome in hepatitis B virus: how can this inform the clinic? Xie N, Chen X, Zhang T, Liu B, Huang C. Expert Rev Proteomics 11 59-74 (2014)
  26. Oncogenic potential of hepatitis B virus encoded proteins. Ringelhan M, Protzer U. Curr Opin Virol 14 109-115 (2015)
  27. Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses. Becker T, Le-Trilling VTK, Trilling M. Int J Mol Sci 20 E1636 (2019)
  28. Tackling hepatitis B virus-associated hepatocellular carcinoma--the future is now. Bharadwaj M, Roy G, Dutta K, Misbah M, Husain M, Hussain S. Cancer Metastasis Rev 32 229-268 (2013)
  29. Antiviral strategies to eliminate hepatitis B virus covalently closed circular DNA (cccDNA). Revill P, Locarnini S. Curr Opin Pharmacol 30 144-150 (2016)
  30. Ubiquitination at the interface of tumor viruses and DNA damage responses. Dybas JM, Herrmann C, Weitzman MD. Curr Opin Virol 32 40-47 (2018)
  31. Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma. Chao CC. World J Hepatol 8 1061-1066 (2016)
  32. Pathogenicity and virulence of Hepatitis B virus. Chuang YC, Tsai KN, Ou JJ. Virulence 13 258-296 (2022)
  33. Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases. Yao J, Liang X, Liu Y, Zheng M. Front Med (Lausanne) 7 586881 (2020)
  34. Tampering of Viruses and Bacteria with Host DNA Repair: Implications for Cellular Transformation. Benedetti F, Curreli S, Gallo RC, Zella D. Cancers (Basel) 13 E241 (2021)
  35. Ubiquitin Proteasome Pathway Transcriptome in Epithelial Ovarian Cancer. Vriend J, Nachtigal MW. Cancers (Basel) 13 2659 (2021)
  36. Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach. Singh P, Kairuz D, Arbuthnot P, Bloom K. World J Gastroenterol 27 3182-3207 (2021)
  37. Strategies to Inhibit Hepatitis B Virus at the Transcript Level. Qu B, Brown RJP. Viruses 13 1327 (2021)
  38. Mechanisms of Viral Degradation of Cellular Signal Transducer and Activator of Transcription 2. Barik S. Int J Mol Sci 23 489 (2022)
  39. Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis. Schollmeier A, Glitscher M, Hildt E. Int J Mol Sci 24 4964 (2023)
  40. Wild type HBx and truncated HBx: Pleiotropic regulators driving sequential genetic and epigenetic steps of hepatocarcinogenesis and progression of HBV-associated neoplasms. Niller HH, Ay E, Banati F, Demcsák A, Takacs M, Minarovits J. Rev Med Virol 26 57-73 (2016)
  41. Current and novel modalities for management of chronic hepatitis B infection. Salama II, Sami SM, Salama SI, Abdel-Latif GA, Shaaban FA, Fouad WA, Abdelmohsen AM, Raslan HM. World J Hepatol 15 585-608 (2023)
  42. Effects of neddylation on viral infection: an overview. Kayesh MEH, Kohara M, Tsukiyama-Kohara K. Arch Virol 169 6 (2023)
  43. Exploiting Ubiquitin Ligases for Induced Target Degradation as an Antiviral Strategy. Verma R. Adv Exp Med Biol 1322 339-357 (2021)
  44. Novel Approaches to Inhibition of HBsAg Expression from cccDNA and Chromosomal Integrants: A Review. Abdelwahed AH, Heineman BD, Wu GY. J Clin Transl Hepatol 11 1485-1497 (2023)
  45. Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions. Villanueva RA, Loyola A. Biomedicines 11 1674 (2023)

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  1. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Fischer ES, Böhm K, Lydeard JR, Yang H, Stadler MB, Cavadini S, Nagel J, Serluca F, Acker V, Lingaraju GM, Tichkule RB, Schebesta M, Forrester WC, Schirle M, Hassiepen U, Ottl J, Hild M, Beckwith RE, Harper JW, Jenkins JL, Thomä NH. Nature 512 49-53 (2014)
  2. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Decorsière A, Mueller H, van Breugel PC, Abdul F, Gerossier L, Beran RK, Livingston CM, Niu C, Fletcher SP, Hantz O, Strubin M. Nature 531 386-389 (2016)
  3. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Fischer ES, Scrima A, Böhm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thomä NH. Cell 147 1024-1039 (2011)
  4. Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Chamberlain PP, Lopez-Girona A, Miller K, Carmel G, Pagarigan B, Chie-Leon B, Rychak E, Corral LG, Ren YJ, Wang M, Riley M, Delker SL, Ito T, Ando H, Mori T, Hirano Y, Handa H, Hakoshima T, Daniel TO, Cathers BE. Nat Struct Mol Biol 21 803-809 (2014)
  5. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Murphy CM, Xu Y, Li F, Nio K, Reszka-Blanco N, Li X, Wu Y, Yu Y, Xiong Y, Su L. Cell Rep 16 2846-2854 (2016)
  6. Structural basis of lentiviral subversion of a cellular protein degradation pathway. Schwefel D, Groom HC, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA. Nature 505 234-238 (2014)
  7. 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. Ahn J, Vu T, Novince Z, Guerrero-Santoro J, Rapic-Otrin V, Gronenborn AM. J Biol Chem 285 37333-37341 (2010)
  8. CBFβ stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression. Kim DY, Kwon E, Hartley PD, Crosby DC, Mann S, Krogan NJ, Gross JD. Mol Cell 49 632-644 (2013)
  9. Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Salerno D, Chiodo L, Alfano V, Floriot O, Cottone G, Paturel A, Pallocca M, Plissonnier ML, Jeddari S, Belloni L, Zeisel M, Levrero M, Guerrieri F. Gut 69 2016-2024 (2020)
  10. Rational discovery of molecular glue degraders via scalable chemical profiling. Mayor-Ruiz C, Bauer S, Brand M, Kozicka Z, Siklos M, Imrichova H, Kaltheuner IH, Hahn E, Seiler K, Koren A, Petzold G, Fellner M, Bock C, Müller AC, Zuber J, Geyer M, Thomä NH, Kubicek S, Winter GE. Nat Chem Biol 16 1199-1207 (2020)
  11. Induction of autophagy and senescence by knockdown of ROC1 E3 ubiquitin ligase to suppress the growth of liver cancer cells. Yang D, Li L, Liu H, Wu L, Luo Z, Li H, Zheng S, Gao H, Chu Y, Sun Y, Liu J, Jia L. Cell Death Differ 20 235-247 (2013)
  12. Inhibition of Hepatitis B virus replication by SAMHD1. Chen Z, Zhu M, Pan X, Zhu Y, Yan H, Jiang T, Shen Y, Dong X, Zheng N, Lu J, Ying S, Shen Y. Biochem Biophys Res Commun 450 1462-1468 (2014)
  13. Methyltransferase PRMT1 is a binding partner of HBx and a negative regulator of hepatitis B virus transcription. Benhenda S, Ducroux A, Rivière L, Sobhian B, Ward MD, Dion S, Hantz O, Protzer U, Michel ML, Benkirane M, Semmes OJ, Buendia MA, Neuveut C. J Virol 87 4360-4371 (2013)
  14. Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. Salsman J, Jagannathan M, Paladino P, Chan PK, Dellaire G, Raught B, Frappier L. J Virol 86 806-820 (2012)
  15. Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal DNA templates. van Breugel PC, Robert EI, Mueller H, Decorsière A, Zoulim F, Hantz O, Strubin M. Hepatology 56 2116-2124 (2012)
  16. The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Wu Y, Zhou X, Barnes CO, DeLucia M, Cohen AE, Gronenborn AM, Ahn J, Calero G. Nat Struct Mol Biol 23 933-940 (2016)
  17. Structural Basis for Substrate Selectivity of the E3 Ligase COP1. Uljon S, Xu X, Durzynska I, Stein S, Adelmant G, Marto JA, Pear WS, Blacklow SC. Structure 24 687-696 (2016)
  18. Detecting remote sequence homology in disordered proteins: discovery of conserved motifs in the N-termini of Mononegavirales phosphoproteins. Karlin D, Belshaw R. PLoS One 7 e31719 (2012)
  19. Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication. Hodgson AJ, Hyser JM, Keasler VV, Cang Y, Slagle BL. Virology 426 73-82 (2012)
  20. Flexible cullins in cullin-RING E3 ligases allosterically regulate ubiquitination. Liu J, Nussinov R. J Biol Chem 286 40934-40942 (2011)
  21. Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation. Lv L, Chen P, Cao L, Li Y, Zeng Z, Cui Y, Wu Q, Li J, Wang JH, Dong MQ, Qi X, Han T. Elife 9 e59994 (2020)
  22. The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses. Suh A, Brosius J, Schmitz J, Kriegs JO. Nat Commun 4 1791 (2013)
  23. Early mesozoic coexistence of amniotes and hepadnaviridae. Suh A, Weber CC, Kehlmaier C, Braun EL, Green RE, Fritz U, Ray DA, Ellegren H. PLoS Genet 10 e1004559 (2014)
  24. Distinct subunit pairing criteria within the heterodimeric IL-12 cytokine family. Jones LL, Chaturvedi V, Uyttenhove C, Van Snick J, Vignali DA. Mol Immunol 51 234-244 (2012)
  25. Hepatitis B virus X protein enhances Myc stability by inhibiting SCF(Skp2) ubiquitin E3 ligase-mediated Myc ubiquitination and contributes to oncogenesis. Lee S, Kim W, Ko C, Ryu WS. Oncogene 35 1857-1867 (2016)
  26. Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx. Jiang T, Liu M, Wu J, Shi Y. Proc Natl Acad Sci U S A 113 2074-2079 (2016)
  27. De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features. Webster E, Cho MT, Alexander N, Desai S, Naidu S, Bekheirnia MR, Lewis A, Retterer K, Juusola J, Chung WK. Cold Spring Harb Mol Case Stud 2 a001172 (2016)
  28. Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals. Abdul F, Filleton F, Gerossier L, Paturel A, Hall J, Strubin M, Etienne L. J Virol 92 e00769-18 (2018)
  29. A first-in-class NAE inhibitor, MLN4924, blocks lentiviral infection in myeloid cells by disrupting neddylation-dependent Vpx-mediated SAMHD1 degradation. Wei W, Guo H, Liu X, Zhang H, Qian L, Luo K, Markham RB, Yu XF. J Virol 88 745-751 (2014)
  30. Hepatitis B Virus X Protein Function Requires Zinc Binding. Ramakrishnan D, Xing W, Beran RK, Chemuru S, Rohrs H, Niedziela-Majka A, Marchand B, Mehra U, Zábranský A, Doležal M, Hubálek M, Pichová I, Gross ML, Kwon HJ, Fletcher SP. J Virol 93 e00250-19 (2019)
  31. Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase. van Hemert FJ, van de Klundert MA, Lukashov VV, Kootstra NA, Berkhout B, Zaaijer HL. PLoS One 6 e23392 (2011)
  32. The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase. Groh BS, Yan F, Smith MD, Yu Y, Chen X, Xiong Y. EMBO Rep 17 638-647 (2016)
  33. Spatiotemporal Analysis of Hepatitis B Virus X Protein in Primary Human Hepatocytes. Kornyeyev D, Ramakrishnan D, Voitenleitner C, Livingston CM, Xing W, Hung M, Kwon HJ, Fletcher SP, Beran RK. J Virol 93 e00248-19 (2019)
  34. The hepatitis B virus x protein inhibits thymine DNA glycosylase initiated base excision repair. van de Klundert MA, van Hemert FJ, Zaaijer HL, Kootstra NA. PLoS One 7 e48940 (2012)
  35. The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β-tent fold. Lupas AN, Zhu H, Korycinski M. PLoS Comput Biol 11 e1004023 (2015)
  36. Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex. Minor MM, Hollinger FB, McNees AL, Jung SY, Jain A, Hyser JM, Bissig KD, Slagle BL. Cells 9 E834 (2020)
  37. DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor. Schabla NM, Mondal K, Swanson PC. J Mol Cell Biol 11 725-735 (2019)
  38. Hepatocyte Factor JMJD5 Regulates Hepatitis B Virus Replication through Interaction with HBx. Kouwaki T, Okamoto T, Ito A, Sugiyama Y, Yamashita K, Suzuki T, Kusakabe S, Hirano J, Fukuhara T, Yamashita A, Saito K, Okuzaki D, Watashi K, Sugiyama M, Yoshio S, Standley DM, Kanto T, Mizokami M, Moriishi K, Matsuura Y. J Virol 90 3530-3542 (2016)
  39. CRL4-like Clr4 complex in Schizosaccharomyces pombe depends on an exposed surface of Dos1 for heterochromatin silencing. Kuscu C, Zaratiegui M, Kim HS, Wah DA, Martienssen RA, Schalch T, Joshua-Tor L. Proc Natl Acad Sci U S A 111 1795-1800 (2014)
  40. DDB1 Stimulates Viral Transcription of Hepatitis B Virus via HBx-Independent Mechanisms. Kim W, Lee S, Son Y, Ko C, Ryu WS. J Virol 90 9644-9653 (2016)
  41. DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication. Kang X, Chen X, He Y, Guo D, Guo L, Zhong J, Shu HB. Virology 435 385-394 (2013)
  42. Defining the interactions and role of DCAF1/VPRBP in the DDB1-cullin4A E3 ubiquitin ligase complex engaged by HIV-1 Vpr to induce a G2 cell cycle arrest. Gérard FC, Yang R, Romani B, Poisson A, Belzile JP, Rougeau N, Cohen ÉA. PLoS One 9 e89195 (2014)
  43. A Mass Spectrometry-Based Profiling of Interactomes of Viral DDB1- and Cullin Ubiquitin Ligase-Binding Proteins Reveals NF-κB Inhibitory Activity of the HIV-2-Encoded Vpx. Landsberg CD, Megger DA, Hotter D, Rückborn MU, Eilbrecht M, Rashidi-Alavijeh J, Howe S, Heinrichs S, Sauter D, Sitek B, Le-Trilling VTK, Trilling M. Front Immunol 9 2978 (2018)
  44. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas. Cho MY, Cheong JY, Lim W, Jo S, Lee Y, Wang HJ, Han KH, Cho H. Oncotarget 5 12233-12246 (2014)
  45. Transgenic mice for cre-inducible overexpression of the Cul4A gene. Li T, Hung MS, Wang Y, Mao JH, Tan JL, Jahan K, Roos H, Xu Z, Jablons DM, You L. Genesis 49 134-141 (2011)
  46. Remarkable Evolutionary Conservation of Antiobesity ADIPOSE/WDTC1 Homologs in Animals and Plants. Ducos E, Vergès V, Dugé de Bernonville T, Blanc N, Giglioli-Guivarc'h N, Dutilleul C. Genetics 207 153-162 (2017)
  47. Targeting Hepatitis B Virus Covalently Closed Circular DNA and Hepatitis B Virus X Protein: Recent Advances and New Approaches. Prescott NA, Bram Y, Schwartz RE, David Y. ACS Infect Dis 5 1657-1667 (2019)
  48. The Antiresection Activity of the X Protein Encoded by Hepatitis Virus B. Ren L, Zeng M, Tang Z, Li M, Wang X, Xu Y, Weng Y, Wang X, Wang H, Guo L, Zuo B, Wang X, Wang S, Lou J, Tang Y, Mu D, Zheng N, Wu X, Han J, Carr AM, Jeggo P, Liu C. Hepatology 69 2546-2561 (2019)
  49. CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation. Lidak T, Baloghova N, Korinek V, Sedlacek R, Balounova J, Kasparek P, Cermak L. Int J Mol Sci 22 5394 (2021)
  50. Hepatitis B Virus Protein X Induces Degradation of Talin-1. van de Klundert MA, van den Biggelaar M, Kootstra NA, Zaaijer HL. Viruses 8 E281 (2016)
  51. Hepatitis: Epigenetic control of HBV by HBx protein--releasing the break? Protzer U. Nat Rev Gastroenterol Hepatol 12 558-559 (2015)
  52. HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver. Yuan H, Zhao L, Yuan Y, Yun H, Zheng W, Geng Y, Yang G, Wang Y, Zhao M, Zhang X. Theranostics 11 8362-8378 (2021)
  53. IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion. Lin H, Yan Y, Luo Y, So WY, Wei X, Zhang X, Yang X, Zhang J, Su Y, Yang X, Zhang B, Zhang K, Jiang N, Chow BKC, Han W, Wang F, Rao F. Nat Commun 12 2461 (2021)
  54. Structural characterization of the BH3-like motif of hepatitis B virus X protein. Kusunoki H, Tanaka T, Kohno T, Wakamatsu K, Hamaguchi I. Biochem Biophys Res Commun 450 741-745 (2014)
  55. An RNAi-based high-throughput screening assay to identify small molecule inhibitors of hepatitis B virus replication. Ghosh S, Kaushik A, Khurana S, Varshney A, Singh AK, Dahiya P, Thakur JK, Sarin SK, Gupta D, Malhotra P, Mukherjee SK, Bhatnagar RK. J Biol Chem 292 12577-12588 (2017)
  56. Proteomic Analysis of Nuclear Hepatitis B Virus Relaxed Circular DNA-Associated Proteins Identifies UV-Damaged DNA Binding Protein as a Host Factor Involved in Covalently Closed Circular DNA Formation. Marchetti AL, Zhang H, Kim ES, Yu X, Jang S, Wang M, Guo H. J Virol 96 e0136021 (2022)
  57. Hepatitis B virus X protein and its host partners. Song H, Xu F, Xiao Q, Tan G. Cell Mol Immunol 18 1345-1346 (2021)
  58. Interactions with DCAF1 and DDB1 in the CRL4 E3 ubiquitin ligase are required for Vpr-mediated G2 arrest. Hakata Y, Miyazawa M, Landau NR. Virol J 11 108 (2014)
  59. Smc5/6 silences episomal transcription by a three-step function. Abdul F, Diman A, Baechler B, Ramakrishnan D, Kornyeyev D, Beran RK, Fletcher SP, Strubin M. Nat Struct Mol Biol 29 922-931 (2022)
  60. Characterization and engineering of broadly reactive monoclonal antibody against hepatitis B virus X protein that blocks its interaction with DDB1. Tao S, Pan S, Gu C, Wei L, Kang N, Xie Y, Liu J. Sci Rep 9 20323 (2019)
  61. Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus. Ma Y, Nakamoto S, Ao J, Qiang N, Kogure T, Ogawa K, Nakagawa M, Fujiwara K, Iwanaga T, Kojima R, Kanzaki H, Koroki K, Kobayashi K, Kanogawa N, Kiyono S, Nakamura M, Kondo T, Nakagawa R, Ogasawara S, Muroyama R, Chiba T, Kato J, Kato N. Int J Mol Sci 23 12015 (2022)
  62. CUL4B facilitates HBV replication by promoting HBx stabilization. Shan H, Wang B, Zhang X, Song H, Li X, Zou Y, Jiang B, Hu H, Dou H, Shao C, Gao L, Ma C, Yang X, Liang X, Gong Y. Cancer Biol Med j.issn.2095-3941.2020.0468 (2021)
  63. Canonical and Divergent N-Terminal HBx Isoform Proteins Unveiled: Characteristics and Roles during HBV Replication. Hernández S, Álvarez-Astudillo F, Garrido D, Prieto C, Loyola A, Villanueva RA. Biomedicines 9 1701 (2021)
  64. Hepatitis B Virus X Protein Is Stabilized by the Deubiquitinating Enzyme VCPIP1 in a Ubiquitin-Independent Manner by Recruiting the 26S Proteasome Subunit PSMC3. Wu Q, Zhang L, Xu X, Zhang Y, Shi J, Lin X, Chen W. J Virol 96 e0061122 (2022)
  65. Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx. He J, Wu J, Chen J, Zhang S, Guo Y, Zhang X, Han J, Zhang Y, Guo Y, Lin Y, Yu W, Kong Y, Shen Z, Mao R, Zhang J. Molecules 27 5000 (2022)
  66. Insight into Viral Hijacking of CRL4 Ubiquitin Ligase through Structural Analysis of the pUL145-DDB1 Complex. Wick ET, Treadway CJ, Li Z, Nicely NI, Ren Z, Baldwin AS, Xiong Y, Harrison JS, Brown NG. J Virol 96 e0082622 (2022)
  67. Pregenomic RNA Launch Hepatitis B Virus Replication System Facilitates the Mechanistic Study of Antiviral Agents and Drug-Resistant Variants on Covalently Closed Circular DNA Synthesis. Zhao Q, Chang J, Rijnbrand R, Lam AM, Sofia MJ, Cuconati A, Guo JT. J Virol 96 e0115022 (2022)
  68. Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor. Le-Trilling VTK, Banchenko S, Paydar D, Leipe PM, Binting L, Lauer S, Graziadei A, Klingen R, Gotthold C, Bürger J, Bracht T, Sitek B, Jan Lebbink R, Malyshkina A, Mielke T, Rappsilber J, Spahn CM, Voigt S, Trilling M, Schwefel D. EMBO J 42 e112351 (2023)
  69. A CRISPR-based system to investigate HBV cccDNA biology. Seeger C. J Virol e0118523 (2023)
  70. Application of fluorescent-based technology detecting protein-protein interactions to monitor the binding of hepatitis B virus X protein to DNA-damage-binding protein 1. Omagari K, Asamitsu K, Tanaka Y. Biophys Physicobiol 18 67-77 (2021)
  71. Characterization of a KDM5 small molecule inhibitor with antiviral activity against hepatitis B virus. Gilmore SA, Tam D, Cheung TL, Snyder C, Farand J, Dick R, Matles M, Feng JY, Ramirez R, Li L, Yu H, Xu Y, Barnes D, Czerwieniec G, Brendza KM, Appleby TC, Birkus G, Willkom M, Kobayashi T, Paoli E, Labelle M, Boesen T, Tay CH, Delaney WE, Notte GT, Schmitz U, Feierbach B. PLoS One 17 e0271145 (2022)
  72. Comment Disruption of HBx-DDB1 by NTZ: New Mechanistic Insight Into an Old Drug With Broad Anti-infective Activities. Su L. Cell Mol Gastroenterol Hepatol 7 289-290 (2019)
  73. Dual role of neddylation in transcription of hepatitis B virus RNAs from cccDNA and production of viral surface antigen. Qu B, Nebioglu F, Leuthold MM, Ni Y, Mutz P, Beneke J, Erfle H, Vondran FWR, Bartenschlager R, Urban S. JHEP Rep 4 100551 (2022)
  74. HBV X Protein Induces Degradation of UBXN7, a Novel Negative Regulator of NF-κB Signaling, to Promote HBV Replication. Yuan S, Xu J, Wang M, Huang J, Ma S, Liu Y, Ke Y, Zeng X, Wu K, Wang J, Tian X, Zheng D, Yousaf T, Naz W, Sun J, Chen L, Guo D, Guo M, Sun G. Cell Mol Gastroenterol Hepatol 15 179-195 (2023)
  75. Hepatitis B Virus Variants with Multiple Insertions and/or Deletions in the X Open Reading Frame 3' End: Common Members of Viral Quasispecies in Chronic Hepatitis B Patients. García-García S, Caballero-Garralda A, Tabernero D, Cortese MF, Gregori J, Rodriguez-Algarra F, Quer J, Riveiro-Barciela M, Homs M, Rando-Segura A, Pacin-Ruiz B, Vila M, Ferrer-Costa R, Pumarola T, Buti M, Rodriguez-Frias F. Biomedicines 10 1194 (2022)
  76. Hepatitis B virus infection disrupts homologous recombination in hepatocellular carcinoma by stabilizing resection inhibitor ADRM1. Zeng M, Tang Z, Ren L, Wang H, Wang X, Zhu W, Mao X, Li Z, Mo X, Chen J, Han J, Kong D, Ji J, Carr AM, Liu C. J Clin Invest 133 e171533 (2023)
  77. Molecular double clips within RepID WD40 domain control chromatin binding and CRL4-substrate assembly. Kim DK, Redon CE, Aladjem MI, Kim HK, Jang SM. Biochem Biophys Res Commun 567 208-214 (2021)
  78. Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome. Liu W, Yao Q, Su X, Deng Y, Yang M, Peng B, Zhao F, Du C, Zhang X, Zhu J, Wang D, Li W, Li H. Nat Commun 14 4663 (2023)
  79. Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates. Raisch J, Dubois ML, Groleau M, Lévesque D, Burger T, Jurkovic CM, Brailly R, Marbach G, McKenna A, Barrette C, Jacques PÉ, Boisvert FM. Mol Cell Proteomics 22 100644 (2023)
  80. Structure of the DDB1-AMBRA1 E3 ligase receptor complex linked to cell cycle regulation. Liu M, Wang Y, Teng F, Mai X, Wang X, Su MY, Stjepanovic G. Nat Commun 14 7631 (2023)
  81. The unique role of the hepatitis virus B X protein on HEK 293 cell morphology and cellular change. Zhang Y, Cheng J, Liu C. Arch Virol 161 1347-1352 (2016)
  82. Transcriptional regulators of human oncoviruses: structural and functional implications for anticancer therapy. Nečasová I, Stojaspal M, Motyčáková E, Brom T, Janovič T, Hofr C. NAR Cancer 4 zcac005 (2022)


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