1887

Abstract

Adenovirus type 5 E1A proteins interact with cellular regulators of transcription to reprogram gene expression in the infected or transformed cell. Although E1A also interacts with DNA directly , it is not clear how this relates to its function . The N-terminal conserved regions 1, 2 and 3 and the C-terminal portions of E1A were prepared as purified recombinant proteins and analyses showed that only the C-terminal region bound DNA . Deletion of E1A amino acids 201–220 inhibited binding and a minimal fragment encompassing amino acids 201–218 of E1A was sufficient for binding single- and double-stranded DNA. This portion of E1A also bound the cation-exchange resins cellulose phosphate and carboxymethyl Sepharose. As this region contains six basic amino acids, binding of E1A to DNA probably results from an ionic interaction with the phosphodiester backbone of DNA. Studies in have shown that expression of a strong transcriptional activation domain fused to a DNA-binding domain can inhibit growth. Although fusion of the C-terminal region of E1A to a strong transcriptional activation domain inhibited growth when expressed in yeast, this was not mediated by the DNA-binding domain identified . These data suggest that E1A does not bind DNA .

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-3-517
2002-03-01
2020-07-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/3/0830517a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-3-517&mimeType=html&fmt=ahah

References

  1. Adams A., Gottschling D. E., Kaiser C. A., Stearns T.. (editors) 1998; Methods in Yeast Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  2. Arany Z., Newsome D., Oldread E., Livingston D. M., Eckner R.. 1995; A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature374:81–84
    [Google Scholar]
  3. Bayley S. T., Mymryk J. S.. 1994; Adenovirus E1A proteins and transformation. International Journal of Oncology5:425–444
    [Google Scholar]
  4. Berger S. L., Pina B., Silverman N., Marcus G. A., Agapite J., Regier J. L., Triezenberg S. J., Guarente L.. 1992; Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell70:251–265
    [Google Scholar]
  5. Boyd J. M., Subramanian T., Schaeper U., La Regina M., Bayley S., Chinnadurai G.. 1993; A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24- ras mediated transformation, tumorigenesis and metastasis. EMBO Journal12:469–478
    [Google Scholar]
  6. Boyer T. G., Berk A. J.. 1993; Functional interaction of adenovirus E1A with holo-TFIID. Genes & Development7:1810–1823
    [Google Scholar]
  7. Chatterjee P. K., Bruner M., Flint S. J., Harter M. L.. 1988; DNA-binding properties of an adenovirus 289R E1A protein. EMBO Journal7:835–841
    [Google Scholar]
  8. Chatton B., Bocco J. L., Gaire M., Hauss C., Reimund B., Goetz J., Kedinger C.. 1993; Transcriptional activation by the adenovirus larger E1a product is mediated by members of the cellular transcription factor ATF family which can directly associate with E1a. Molecular and Cellular Biology13:561–570
    [Google Scholar]
  9. Dyson N., Harlow E.. 1992; Adenovirus E1A targets key regulators of cell proliferation. Cancer Surveillance12:161–195
    [Google Scholar]
  10. Eckner R., Ewen M. E., Newsome D., Gerdes M., DeCaprio J. A., Lawrence J. B., Livingston D. M.. 1994; Molecular cloning and functional analysis of the adenovirus E1A- associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes & Development8:869–884
    [Google Scholar]
  11. Egan C., Bayley S. T., Branton P. E.. 1989; Binding of the Rb1 protein to E1A products is required for adenovirus transformation. Oncogene4:383–388
    [Google Scholar]
  12. Ewen M. E., Xing Y. G., Lawrence J. B., Livingston D. M.. 1991; Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell66:1155–1164
    [Google Scholar]
  13. Geisberg J. V., Lee W. S., Berk A. J., Ricciardi R. P.. 1994; The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein. Proceedings of the National Academy of Sciences, USA91:2488–2492
    [Google Scholar]
  14. Geisberg J. V., Chen J. L., Ricciardi R. P.. 1995; Subregions of the adenovirus E1A transactivation domain target multiple components of the TFIID complex. Molecular and Cellular Biology15:6283–6290
    [Google Scholar]
  15. Hannon G. J., Demetrick D., Beach D.. 1993; Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes & Development7:2378–2391
    [Google Scholar]
  16. Hateboer G., Timmers H. T. M., Rustgi A. K., Billaud M., van’t Veer L. J., Bernards R.. 1993; TATA-binding protein and the retinoblastoma gene product bind to overlapping epitopes on c-Myc and adenovirus E1A protein. Proceedings of the National Academy of Sciences, USA90:8489–8493
    [Google Scholar]
  17. Jelsma T. N., Howe J. A., Evelegh C. M., Cunniff N. F., Skiadopoulos M. H., Floroff M. R., Denman J. E., Bayley S. T.. 1988; 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. Virology163:494–502
    [Google Scholar]
  18. Kimelman D., Miller J. S., Porter D., Roberts B. E.. 1985; E1a regions of the human adenoviruses and of the highly oncogenic simian adenovirus 7 are closely related. Journal of Virology53:399–409
    [Google Scholar]
  19. Liu F., Green M. R.. 1994; Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains. Nature368:520–525
    [Google Scholar]
  20. Lundblad J. R., Kwok R. P., Laurance M. E., Harter M. L., Goodman R. H.. 1995; Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature374:85–88
    [Google Scholar]
  21. Maguire K., Shi X. P., Horikoshi N., Rappaport J., Rosenberg M., Weinmann R.. 1991; Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors. Oncogene6:1417–1422
    [Google Scholar]
  22. Marcus G. A., Horiuchi J., Silverman N., Guarente L.. 1996; ADA5/SPT20 links the ADA and SPT genes, which are involved in yeast transcription. Molecular and Cellular Biology16:3197–3205
    [Google Scholar]
  23. Mazzarelli J. M., Atkins G. B., Geisberg J. V., Ricciardi R. P.. 1995; The viral oncoproteins Ad5 E1A, HPV16 E7 and SV40 TAg bind a common region of the TBP-associated factor-110. Oncogene11:1859–1864
    [Google Scholar]
  24. Moran E.. 1994; Cell growth control mechanisms reflected through protein interactions with the adenovirus E1A gene products. Seminars in Virology5:327–340
    [Google Scholar]
  25. Peeper D. S., Zantema A.. 1993; Adenovirus-E1A proteins transform cells by sequestering regulatory proteins. Molecular Biology Reports17:197–207
    [Google Scholar]
  26. Pina B., Berger S., Marcus G. A., Silverman N., Agapite J., Guarente L.. 1993; ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2. Molecular and Cellular Biology13:5981–5989
    [Google Scholar]
  27. Roberts S. M., Winston F.. 1997; Essential functional interactions of SAGA, a Saccharomyces cerevisiae complex of Spt, Ada, and Gcn5 proteins, with the Snf/Swi and Srb/mediator complexes. Genetics147:451–465
    [Google Scholar]
  28. Schaeper U., Boyd J. M., Verma S., Uhlmann E., Subramanian T., Chinnadurai G.. 1995; Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation. Proceedings of the National Academy of Sciences, USA92:10467–10471
    [Google Scholar]
  29. Shenk T., Flint J.. 1991; Transcriptional and transforming activities of the adenovirus E1A proteins. Advances in Cancer Research57:47–85
    [Google Scholar]
  30. Song C. Z., Loewenstein P. M., Toth K., Green M.. 1995; Transcription factor TFIID is a direct functional target of the adenovirus E1A transcription-repression domain. Proceedings of the National Academy of Sciences, USA92:10330–10333
    [Google Scholar]
  31. van Ormondt H., Maat J., Dijkema R.. 1986; Comparison of nucleotide sequences of the early E1a regions for subgroups A, B, and C of human adenoviruses. Gene12:63–76
    [Google Scholar]
  32. Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E.. 1988; Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature334:124–129
    [Google Scholar]
  33. Yang X. J., Ogryzko V. V., Nishikawa J., Howard B. H., Nakatani Y.. 1996; A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature382:319–324
    [Google Scholar]
  34. Zhang Z., Smith M. M., Mymryk J. S.. 2001; Interaction of the E1A oncoprotein with Yak1p, a novel regulator of yeast pseudohyphal differentiation, and related mammalian kinases. Molecular and Cellular Biology12:699–710
    [Google Scholar]
  35. Zu Y.-L., Takamatsu Y., Zhao M.-J., Maekawa T., Handa H., Ishii S.. 1992; Transcriptional regulation by a point mutant of adenovirus-2 E1a product lacking DNA binding activity. Journal of Biological Chemistry267:20181–20187
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-3-517
Loading
/content/journal/jgv/10.1099/0022-1317-83-3-517
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error