adenovirus early proteins


Summary: Proteins encoded by adenoviruses that are synthesized prior to, and in the absence of, viral DNA replication. The proteins are involved in both positive and negative regulation of expression in viral and cellular genes, and also affect the stability of viral mRNA. Some are also involved in oncogenic transformation.

Top Publications

  1. Lillie J, Green M. Transcription activation by the adenovirus E1a protein. Nature. 1989;338:39-44 pubmed
  2. La Thangue N, Thimmappaya B, Rigby P. The embryonal carcinoma stem cell Ela-like activity involves a differentiation-regulated transcription factor. Nucleic Acids Res. 1990;18:2929-38 pubmed
  3. Spessot R, Inchley K, Hupel T, Bacchetti S. Cloning of the herpes simplex virus ICP4 gene in an adenovirus vector: effects on adenovirus gene expression and replication. Virology. 1989;168:378-87 pubmed
    ..Our results indicate that ICP4 does not possess all of the functions of the E1a proteins and, furthermore, that adenovirus early genes differ in their susceptibility to heterologous trans-activators. ..
  4. Jansen Durr P, Wintzerith M, Reimund B, Hauss C, Kedinger C. Two distinct cellular proteins interact with the EIa-responsive element of an adenovirus early promoter. J Virol. 1990;64:2384-7 pubmed
    ..The possible involvement of C alpha in the EIa responsiveness of this promoter is discussed. ..
  5. Yamasaki L, Kanda P, Lanford R. Identification of four nuclear transport signal-binding proteins that interact with diverse transport signals. Mol Cell Biol. 1989;9:3028-36 pubmed
    ..The four proteins were not bound by wheat germ agglutinin and were not associated tightly with the nuclear pore complex. ..
  6. White E, Spector D, Welch W. Differential distribution of the adenovirus E1A proteins and colocalization of E1A with the 70-kilodalton cellular heat shock protein in infected cells. J Virol. 1988;62:4153-66 pubmed
    ..The relevance of this association, with respect to the function of these proteins during infection and the association of other oncoproteins with hsp70, is discussed. ..
  7. Mantzaris G, Priddle J, Jewell D. T lymphocyte responses to a synthetic peptide from the human intestinal adenovirus 12 in coeliac disease. J Clin Lab Immunol. 1990;31:75-9 pubmed
    ..It also offers further evidence for the possible implication of adenovirus 12 in the pathogenesis of coeliac disease. ..
  8. Datta S, Soong C, Wang D, Harter M. A purified adenovirus 289-amino-acid E1A protein activates RNA polymerase III transcription in vitro and alters transcription factor TFIIIC. J Virol. 1991;65:5297-304 pubmed
    ..These results clearly establish that E1A mediates its effect on VA1 transcription through TFIIIC in a very rapid yet indirect manner.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  9. Sanai Y, Oda K, Nagai Y. Induction of GD3 ganglioside by adenovirus E1A gene 13S- and 12S-mRNA products in rat 3Y1 cells. J Biochem. 1990;107:740-2 pubmed
    ..Ganglioside GM2 was also accumulated by induction of 13S-mRNA of adenovirus E1A gene. The results indicated that 13S- or 12S-mRNA product alone has the ability to induce GD3 ganglioside in rat 3Y1 cells. ..

More Information


  1. Knebel Mörsdorf D, Achten S, Langner K, Rüger R, Fleckenstein B, Doerfler W. Reactivation of the methylation-inhibited late E2A promoter of adenovirus type 2 by a strong enhancer of human cytomegalovirus. Virology. 1988;166:166-74 pubmed
    ..Weisshaar et al., 1988, J. Mol. Biol. 202, 255-270). Thus there are several ways in which a methylated and silenced promoter can be reactivated in mammalian cells. ..
  2. Cone R, Grodzicker T, Jaramillo M. A retrovirus expressing the 12S adenoviral E1A gene product can immortalize epithelial cells from a broad range of rat tissues. Mol Cell Biol. 1988;8:1036-44 pubmed
    ..J. Berk, J. Virol. 53:742-750, 1985), in which the 12S E1A protein is required for the complete induction of the cellular DNA replication machinery in the quiescent human epithelial cells in which adenoviruses normally replicate. ..
  3. Grant M, Bruton R, Byrd P, Gallimore P, Steele J, Taylor A, et al. Sensitivity to ionising radiation of transformed human cells containing mutant ras genes. Oncogene. 1990;5:1159-64 pubmed
    ..It may be interesting to note, however, that two out of the three ras transformants which were least sensitive to gamma-rays were cell lines expressing the highest levels of p21. ..
  4. Herbst R, Pelletier M, Boczko E, Babiss L. The state of cellular differentiation determines the activity of the adenovirus E1A enhancer element: evidence for negative regulation of enhancer function. J Virol. 1990;64:161-72 pubmed
  5. Hoeveler A, Doerfler W. Specific factors binding to the late E2A promoter region of adenovirus type 2 DNA: no apparent effects of 5'-CCGG-3' methylation. DNA. 1987;6:449-60 pubmed
  6. Hitt M, Graham F. Adenovirus E1A under the control of heterologous promoters: wide variation in E1A expression levels has little effect on virus replication. Virology. 1990;179:667-78 pubmed
    ..These results suggest that very low levels of E1A proteins are sufficient for virus production in cultured cells and that wild-type Ad 5 produces an amount of E1A in excess of that required. ..
  7. Gorman C, Gies D, McCray G, Huang M. The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins. Virology. 1989;171:377-85 pubmed
    ..Increases in expression due to E1a and E1b proteins were additive. These results suggest that adenovirus early expression can activate quiescent HCMV sequences. ..
  8. Kaelin W, Pallas D, DeCaprio J, Kaye F, Livingston D. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991;64:521-32 pubmed
    ..Therefore, the binding of one or more of these proteins may contribute to the growth-suppressing function of pRB. ..
  9. Kovelman R, Roeder R. Sarkosyl defines three intermediate steps in transcription initiation by RNA polymerase III: application to stimulation of transcription by E1A. Genes Dev. 1990;4:646-58 pubmed
    ..Using 0.05% Sarkosyl to limit reinitiation, we determined that the E1A-mediated stimulation of transcription by RNA polymerase III resulted from an increase in the number of active transcription complexes. ..
  10. Bernard B, Bailly C, Lenoir M, Darmon M. Modulation of HPV18 and BPV1 transcription in human keratinocytes by simian virus 40 large T antigen and adenovirus type 5 E1A antigen. J Cell Biochem. 1990;42:101-10 pubmed
    ..The 230 bp Rsa1-Rsa1 central domain of the HPV18-LCR seems involved both in transcriptional stimulation by SV40 large T antigen and transcriptional inhibition by adenovirus E1a antigen. ..
  11. Moran E. A region of SV40 large T antigen can substitute for a transforming domain of the adenovirus E1A products. Nature. 1988;334:168-70 pubmed
  12. Kuppuswamy M, Chinnadurai G. Cell type dependent transformation by adenovirus 5 E1a proteins. Oncogene. 1988;2:567-72 pubmed
    ..Our results suggest that the unique region of the 289R protein has the potential to inhibit immortalization of primary epithelial cells. ..
  13. Mantzaris G, Karagiannis J, Priddle J, Jewell D. Cellular hypersensitivity to a synthetic dodecapeptide derived from human adenovirus 12 which resembles a sequence of A-gliadin in patients with coeliac disease. Gut. 1990;31:668-73 pubmed
    ..This antigenic cross reactivity may be involved in the pathogenesis of coeliac disease. ..
  14. Tremblay M, Dumont D, Branton P. Analysis of phosphorylation sites in the exon 1 region of E1A proteins of human adenovirus type 5. Virology. 1989;169:397-407 pubmed
    ..However, neither site appears to be of major importance in the regulation of E1A-mediated transactivation or transformation. ..
  15. Tan T, Jia R, Roeder R. Utilization of signal transduction pathway by the human T-cell leukemia virus type I transcriptional activator tax. J Virol. 1989;63:3761-8 pubmed
  16. Whyte P, Williamson N, Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 1989;56:67-75 pubmed
    ..These results suggest that the interactions with these cellular proteins are fundamental to the transforming activity of E1A. ..
  17. Kaddurah Daouk R, Lillie J, Daouk G, Green M, Kingston R, Schimmel P. Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a. Mol Cell Biol. 1990;10:1476-83 pubmed
    ..The induction by an oncogene of a cellular gene for energy metabolism may be of significance for the metabolic events that take place after oncogenic activation. ..
  18. Mudryj M, Hiebert S, Nevins J. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990;9:2179-84 pubmed
    ..We also believe that the E2F transcription factor is the first example of a regulator of the class of immediate early genes that is slowly activated by stimulation of cell proliferation. ..
  19. Smith C, Debouck C, Rosenberg M, Culp J. Phosphorylation of serine residue 89 of human adenovirus E1A proteins is responsible for their characteristic electrophoretic mobility shifts, and its mutation affects biological function. J Virol. 1989;63:1569-77 pubmed
    ..The relevance of phosphorylation to structure and activity of E1A and other nuclear oncogene proteins is discussed. ..
  20. Reddy P, Idamakanti N, Song J, Lee J, Hyun B, Park J, et al. Sequence and transcription map analysis of early region-1 of porcine adenovirus type-3. Virus Res. 1998;58:97-106 pubmed
    ..In PAV-3, the gene coding for pIX is located between 9.9 and 12.2 map units and codes for a protein of 199 amino acids. ..
  21. Lassar A, Davis R, Wright W, Kadesch T, Murre C, Voronova A, et al. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991;66:305-15 pubmed
    ..In addition we demonstrate that MyoD, in conjunction with E12/E47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators. ..
  22. Brockmann D, Schmidtmann A, Furst S, Tries B, Esche H. Cloning of adenovirus type 12 E1 genes into a retroviral vector and their differential splicing in mouse cells. Gene. 1990;91:167-72 pubmed
    ..These results demonstrate that the ratio of genomic vs. subgenomic retroviral RNAs of Ad12 E1-carrying vectors is dependent on the cloned insert and the cell system used. ..
  23. de Groot R, Meijer I, van den Brink S, Mummery C, Kruijer W. Differential regulation of JunB and JunD by adenovirus type 5 and 12 E1A proteins. Oncogene. 1991;6:2357-61 pubmed
    ..Interestingly, E1A12 expression leads to complete differentiation of P19 EC cells, comparable to the effect of RA on these cells, while E1A5-expressing cells are only partially differentiated. ..
  24. Leong K, Brunet L, Berk A. Factors responsible for the higher transcriptional activity of extracts of adenovirus-infected cells fractionate with the TATA box transcription factor. Mol Cell Biol. 1988;8:1765-74 pubmed
    ..Other models consistent with the results are also discussed. ..
  25. Jackson P, Bellett A. Relationship between organization of the actin cytoskeleton and the cell cycle in normal and adenovirus-infected rat cells. J Virol. 1989;63:311-8 pubmed
    ..Thus, disruption of the actin cytoskeleton is an early effect of E1A and not an indirect consequence of the entry of infected cells into the cell cycle. ..
  26. Eloit M, Gilardi Hebenstreit P, Toma B, Perricaudet M. Construction of a defective adenovirus vector expressing the pseudorabies virus glycoprotein gp50 and its use as a live vaccine. J Gen Virol. 1990;71 ( Pt 10):2425-31 pubmed
    ..Rabbits and mice inoculated with Ad-gp50 showed a strong antibody response against gp50. Some of them were protected from a virulent challenge with pseudorabies virus. ..
  27. Bruder J, Hearing P. Cooperative binding of EF-1A to the E1A enhancer region mediates synergistic effects on E1A transcription during adenovirus infection. J Virol. 1991;65:5084-7 pubmed
    ..In this report, we demonstrate that the cooperative binding of EF-1A to neighboring sites in the E1A enhancer region results in a synergistic activation of E1A transcription in infected cells. ..
  28. Williams J, Garcia J, Harrich D, Pearson L, Wu F, Gaynor R. Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs. EMBO J. 1990;9:4435-42 pubmed
    ..abstract truncated at 250 words) ..
  29. Rodrigues M, Dion P, Sircar S, Weber J. Tumor necrosis factor mediated cytolysis requires the adenovirus E1a protein but not the transformed phenotype. Virus Res. 1990;15:231-6 pubmed
    ..The results showed that TNF did not affect either E1a or c-myc transcription in our cells during the development of the cytotoxic response. ..
  30. Ackrill A, Foster G, Laxton C, Flavell D, Stark G, Kerr I. Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene. Nucleic Acids Res. 1991;19:4387-93 pubmed
    ..An essential component(s) of a number of signalling pathways must, therefore, be subject, directly or indirectly, to inhibition by E1A. ..
  31. Lavery D, Chen Kiang S. Adenovirus E1A and E1B genes are regulated posttranscriptionally in human lymphoid cells. J Virol. 1990;64:5349-59 pubmed
    ..Lavery, S. M. Fu, T. Lufkin, and S. Chen-Kiang, J. Virol. 61:1466-1472, 1987). The molecular mechanisms by which E1A and E1B are regulated and by which E1A transactivates viral genes in lymphoid cells are discussed. ..
  32. Uchio E, Matsuura N, Takeuchi S, Itoh N, Ishiko H, Aoki K, et al. Acute follicular conjunctivitis caused by adenovirus type 34. Am J Ophthalmol. 1999;128:680-6 pubmed
    ..These results indicate that adenovirus 34 may induce acute conjunctivitis in immunocompetent subjects and that special attention should be paid to adenovirus 34 as a causative agent for adenoviral conjunctivitis. ..
  33. Hu Q, Dyson N, Harlow E. The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations. EMBO J. 1990;9:1147-55 pubmed
    ..These results strongly suggest that these viral oncoproteins are targeting a protein domain that is an important site in the normal function of the RB protein. ..
  34. Hiebert S, Blake M, Azizkhan J, Nevins J. Role of E2F transcription factor in E1A-mediated trans activation of cellular genes. J Virol. 1991;65:3547-52 pubmed
    ..Moreover, since the products of most of these genes are likely critical for cellular proliferation, there are obvious consequences of this trans activation for cellular phenotype. ..
  35. Goding C, Temperley S, Fisher F. Multiple transcription factors interact with the adenovirus-2 EII-late promoter: evidence for a novel CCAAT recognition factor. Nucleic Acids Res. 1987;15:7761-80 pubmed
    ..Finally, an additional factor recognising the consensus GGGGGGNT has been detected. ..
  36. Picard D, Salser S, Yamamoto K. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell. 1988;54:1073-80 pubmed
    ..We speculate that the inhibitory effect of the unliganded steroid binding domain may be mediated by heat shock protein hsp90, which binds selectively to the unliganded receptor. ..
  37. Higashimoto Y, Yamagata Y, Itoh H. Complex effect of adenovirus early region proteins on innate immune system. Inflamm Allergy Drug Targets. 2006;5:229-37 pubmed
    ..Understanding the roles of the Ad gene products in the induction and inhibition of innate inflammatory functions will help us to clarify the pathogenesis of the chronic respiratory illness including COPD. ..
  38. Xing L, Tikoo S. Porcine adenovirus type 3 E1 transcriptional control region contains a bifunctional regulatory element. Virology. 2004;318:37-44 pubmed
    ..The results indicated that the upstream activation sequences (UAS) of E1A overlap the upstream repression sequences (URS) of E1B, although both transcription units are transcribed from different promoters...
  39. Dragulev B, Sira S, AbouHaidar M, Campbell J. Sequence analysis of putative E3 and fiber genomic regions of two strains of canine adenovirus type 1. Virology. 1991;183:298-305 pubmed
    ..The suggestion is made that the attenuation of the CLL strain may be related to the nonfunctionality of its E3 gene product(s). ..
  40. Mautner V, Mackay N. Enteric adenovirus type 40: complementation of the E4 defect in Ad2 dl808. Virology. 1991;183:433-6 pubmed
    ..Surprisingly, Ad2 dl808 fails to reciprocally complement Ad40. The results show that Ad40 produces functional E4 ORF 6 and/or ORF 3 activity, and that their expression precedes DNA replication. ..
  41. Ohshima T. [Roles of tumor suppressor genes in human osteosarcoma cells]. Kokubyo Gakkai Zasshi. 1991;58:300-18 pubmed
    ..These results further confirm that inactivating mutations of p53 and RB genes are deeply involved in the carcinogenesis of human osteosarcoma and suggest that p107 and p300 may not play a role in the tumorigenesis. ..
  42. Cook J, Lewis A, Klimkait T, Knust B, Doerfler W, Walker T. In vivo evolution of adenovirus 2-transformed cell virulence associated with altered E1A gene function. Virology. 1988;163:374-90 pubmed
    ..The data suggest that an interruption in cellular pathways of E1A expression may result in increased transformed cell virulence. ..
  43. Simon M, Rooney R, Fisch T, Heintz N, Nevins J. E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence. Proc Natl Acad Sci U S A. 1990;87:513-7 pubmed
    ..We conclude that the E1A-dependent activation of c-fos transcription is mediated through an effect on a TATA-binding protein that has specificity for the TATAA sequence. ..
  44. Burgert H, Kvist S. The E3/19K protein of adenovirus type 2 binds to the domains of histocompatibility antigens required for CTL recognition. EMBO J. 1987;6:2019-26 pubmed
    ..Interestingly, these domains are also crucial for T cell recognition. The implications for the evolution of adenoviruses and their ability to cause persistent infections are discussed. ..
  45. Bridge E, Ketner G. Interaction of adenoviral E4 and E1b products in late gene expression. Virology. 1990;174:345-53 pubmed
    ..Pilder, M. Moore, J. Logan, and T. Shenk, 1986, Mol. Cell. Biol. 6, 470-476). Finally the 116R protein seems to act in parallel with the complex to permit normal viral DNA replication. ..
  46. Jelsma T, Howe J, Evelegh C, Cunniff N, Skiadopoulos M, Floroff M, et al. Use of deletion and point mutants spanning the coding region of the adenovirus 5 E1A gene to define a domain that is essential for transcriptional activation. Virology. 1988;163:494-502 pubmed
    ..The results obtained with these mutants are discussed in relation to the transactivation obtained by J. W. Lillie et al. [(1987). Cell 50, 1091-1100] with a synthetic peptide similar to the domain described here. ..
  47. Ulfendahl P, Linder S, Kreivi J, Nordqvist K, Sevensson C, Hultberg H, et al. A novel adenovirus-2 E1A mRNA encoding a protein with transcription activation properties. EMBO J. 1987;6:2037-44 pubmed
  48. Ventura A, Arens M, Srinivasan A, Chinnadurai G. Silencing of human immunodeficiency virus long terminal repeat expression by an adenovirus E1a mutant. Proc Natl Acad Sci U S A. 1990;87:1310-4 pubmed
    ..Cotransfection of HIV-1 proviral DNA with hr5 DNA resulted in a significant reduction of HIV production. ..
  49. Vanhaesebroeck B, Timmers H, Pronk G, van Roy F, van der Eb A, Fiers W. Modulation of cellular susceptibility to the cytotoxic/cytostatic action of tumor necrosis factor by adenovirus E1 gene expression is cell type-dependent. Virology. 1990;176:362-8 pubmed
    ..Differences in E1A expression levels between cell types cannot explain this discrepancy regarding modulation of TNF sensitivity by E1A. ..
  50. Adami G, Babiss L. The efficiency of adenovirus transformation of rodent cells is inversely related to the rate of viral E1A gene expression. J Virol. 1990;64:3427-36 pubmed
    ..Our findings suggest that the process leading to a fully transformed cell involves multiple stages, with an early stage being facilitated by a reduced rate of viral E1A gene expression. ..
  51. Roy S, Gao G, Clawson D, Vandenberghe L, Farina S, Wilson J. Complete nucleotide sequences and genome organization of four chimpanzee adenoviruses. Virology. 2004;324:361-72 pubmed
    ..Analysis of the capsid proteins hexon and fiber of the chimpanzee adenoviruses also supports the placement of Simian Adenovirus 21 in subgroup B and Simian Adenoviruses 22, 23, and 24 in subgroup E...
  52. Gooding L, Ranheim T, Tollefson A, Aquino L, Duerksen Hughes P, Horton T, et al. The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus function together to protect many but not all mouse cell lines against lysis by tumor necrosis factor. J Virol. 1991;65:4114-23 pubmed
    ..Considering that three sets of proteins (E3 14.7K, E1B 19K, and E3 10.4K/14.5K proteins) exist in adenovirus to prevent TNF cytolysis of different cell types, it would appear that TNF is a major antiadenovirus defense of the host. ..
  53. Werness B, Levine A, Howley P. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248:76-9 pubmed