• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Jan 1993; 13(1): 561–570.
PMCID: PMC358935

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.

Abstract

We recently isolated three cDNA clones encoding closely related proteins (ATFa1, ATFa2, and ATFa3) that belong to the activating transcription factor-cyclic AMP-responsive element family of cellular transcription factors. Using cotransfection experiments, we showed that these proteins mediate the transcriptional activation induced by the adenovirus E1a 13S mRNA gene product and that the zinc-binding domains present in both E1a conserved region 3 and the most N-terminal portion of the ATFa proteins play crucial roles in this activity. Reciprocal coimmunoprecipitation experiments demonstrated direct interactions between these proteins. Neither the conserved region 3 domain of E1a nor the N-terminal metal-binding element of ATFa is essential for these interactions. The simultaneous alteration of both the N-terminal and the C-terminal domains of ATFa abolished E1a binding, while either mutation alone failed to impair these interactions.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bagchi S, Weinmann R, Raychaudhuri P. The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F. Cell. 1991 Jun 14;65(6):1063–1072. [PubMed]
  • Bandara LR, Adamczewski JP, Hunt T, La Thangue NB. Cyclin A and the retinoblastoma gene product complex with a common transcription factor. Nature. 1991 Jul 18;352(6332):249–251. [PubMed]
  • Bandara LR, La Thangue NB. Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature. 1991 Jun 6;351(6326):494–497. [PubMed]
  • Banerji J, Rusconi S, Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. [PubMed]
  • Berk AJ. Adenovirus promoters and E1A transactivation. Annu Rev Genet. 1986;20:45–79. [PubMed]
  • Berkowitz LA, Gilman MZ. Two distinct forms of active transcription factor CREB (cAMP response element binding protein). Proc Natl Acad Sci U S A. 1990 Jul;87(14):5258–5262. [PMC free article] [PubMed]
  • Braithwaite AW, Nelson CC, Bellett AJ. E1a revisited: the case for multiple cooperative trans-activation domains. New Biol. 1991 Jan;3(1):18–26. [PubMed]
  • Chatterjee PK, Bruner M, Flint SJ, Harter ML. DNA-binding properties of an adenovirus 289R E1A protein. EMBO J. 1988 Mar;7(3):835–841. [PMC free article] [PubMed]
  • Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR. The E2F transcription factor is a cellular target for the RB protein. Cell. 1991 Jun 14;65(6):1053–1061. [PubMed]
  • Chittenden T, Livingston DM, Kaelin WG., Jr The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein. Cell. 1991 Jun 14;65(6):1073–1082. [PubMed]
  • Culp JS, Webster LC, Friedman DJ, Smith CL, Huang WJ, Wu FY, Rosenberg M, Ricciardi RP. The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6450–6454. [PMC free article] [PubMed]
  • Evans RM, Hollenberg SM. Zinc fingers: gilt by association. Cell. 1988 Jan 15;52(1):1–3. [PubMed]
  • Ferguson B, Krippl B, Andrisani O, Jones N, Westphal H, Rosenberg M. E1A 13S and 12S mRNA products made in Escherichia coli both function as nucleus-localized transcription activators but do not directly bind DNA. Mol Cell Biol. 1985 Oct;5(10):2653–2661. [PMC free article] [PubMed]
  • Flint KJ, Jones NC. Differential regulation of three members of the ATF/CREB family of DNA-binding proteins. Oncogene. 1991 Nov;6(11):2019–2026. [PubMed]
  • Flint J, Shenk T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. [PubMed]
  • Frankel AD, Chen L, Cotter RJ, Pabo CO. Dimerization of the tat protein from human immunodeficiency virus: a cysteine-rich peptide mimics the normal metal-linked dimer interface. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6297–6300. [PMC free article] [PubMed]
  • Gaire M, Chatton B, Kedinger C. Isolation and characterization of two novel, closely related ATF cDNA clones from HeLa cells. Nucleic Acids Res. 1990 Jun 25;18(12):3467–3473. [PMC free article] [PubMed]
  • Giordano A, Whyte P, Harlow E, Franza BR, Jr, Beach D, Draetta G. A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells. Cell. 1989 Sep 8;58(5):981–990. [PubMed]
  • Gonzalez GA, Yamamoto KK, Fischer WH, Karr D, Menzel P, Biggs W, 3rd, Vale WW, Montminy MR. A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence. Nature. 1989 Feb 23;337(6209):749–752. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Green S, Issemann I, Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. [PMC free article] [PubMed]
  • Hai TW, Liu F, Coukos WJ, Green MR. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. [PubMed]
  • Harlow E, Whyte P, Franza BR, Jr, Schley C. Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol. 1986 May;6(5):1579–1589. [PMC free article] [PubMed]
  • Hoeffler JP, Meyer TE, Yun Y, Jameson JL, Habener JF. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988 Dec 9;242(4884):1430–1433. [PubMed]
  • Honzatko RB, Crawford JL, Monaco HL, Ladner JE, Ewards BF, Evans DR, Warren SG, Wiley DC, Ladner RC, Lipscomb WN. Crystal and molecular structures of native and CTP-liganded aspartate carbamoyltransferase from Escherichia coli. J Mol Biol. 1982 Sep 15;160(2):219–263. [PubMed]
  • Horikoshi M, Hai T, Lin YS, Green MR, Roeder RG. Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex. Cell. 1988 Sep 23;54(7):1033–1042. [PubMed]
  • Horikoshi N, Maguire K, Kralli A, Maldonado E, Reinberg D, Weinmann R. Direct interaction between adenovirus E1A protein and the TATA box binding transcription factor IID. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5124–5128. [PMC free article] [PubMed]
  • Hurst HC, Totty NF, Jones NC. Identification and functional characterisation of the cellular activating transcription factor 43 (ATF-43) protein. Nucleic Acids Res. 1991 Sep 11;19(17):4601–4609. [PMC free article] [PubMed]
  • Imperiale MJ, Nevins JR. Adenovirus 5 E2 transcription unit: an E1A-inducible promoter with an essential element that functions independently of position or orientation. Mol Cell Biol. 1984 May;4(5):875–882. [PMC free article] [PubMed]
  • Ivashkiv LB, Liou HC, Kara CJ, Lamph WW, Verma IM, Glimcher LH. mXBP/CRE-BP2 and c-Jun form a complex which binds to the cyclic AMP, but not to the 12-O-tetradecanoylphorbol-13-acetate, response element. Mol Cell Biol. 1990 Apr;10(4):1609–1621. [PMC free article] [PubMed]
  • Jones C, Lee KA. E1A-mediated activation of the adenovirus E4 promoter can occur independently of the cellular transcription factor E4F. Mol Cell Biol. 1991 Sep;11(9):4297–4305. [PMC free article] [PubMed]
  • Jones NC, Rigby PW, Ziff EB. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. [PubMed]
  • Krippl B, Ferguson B, Rosenberg M, Westphal H. Functions of purified E1A protein microinjected into mammalian cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6988–6992. [PMC free article] [PubMed]
  • Kunkel TA, Roberts JD, Zakour RA. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Lee WS, Kao CC, Bryant GO, Liu X, Berk AJ. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. [PubMed]
  • Leff T, Elkaim R, Goding CR, Jalinot P, Sassone-Corsi P, Perricaudet M, Kédinger C, Chambon P. Individual products of the adenovirus 12S and 13S EIa mRNAs stimulate viral EIIa and EIII expression at the transcriptional level. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4381–4385. [PMC free article] [PubMed]
  • Lillie JW, Green MR. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. [PubMed]
  • Liou HC, Boothby MR, Finn PW, Davidon R, Nabavi N, Zeleznik-Le NJ, Ting JP, Glimcher LH. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 1990 Mar 30;247(4950):1581–1584. [PubMed]
  • Liu F, Green MR. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. [PubMed]
  • Maekawa T, Matsuda S, Fujisawa J, Yoshida M, Ishii S. Cyclic AMP response element-binding protein, CRE-BP1, mediates the E1A-induced but not the Tax-induced trans-activation. Oncogene. 1991 Apr;6(4):627–632. [PubMed]
  • Maekawa T, Sakura H, Kanei-Ishii C, Sudo T, Yoshimura T, Fujisawa J, Yoshida M, Ishii S. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989 Jul;8(7):2023–2028. [PMC free article] [PubMed]
  • Maguire K, Shi XP, Horikoshi N, Rappaport J, Rosenberg M, Weinmann R. Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors. Oncogene. 1991 Aug;6(8):1417–1422. [PubMed]
  • Martin KJ, Lillie JW, Green MR. Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets. Nature. 1990 Jul 12;346(6280):147–152. [PubMed]
  • Mazen A, Gradwohl G, de Murcia G. Zinc-binding proteins detected by protein blotting. Anal Biochem. 1988 Jul;172(1):39–42. [PubMed]
  • Moran E, Mathews MB. Multiple functional domains in the adenovirus E1A gene. Cell. 1987 Jan 30;48(2):177–178. [PubMed]
  • Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991 Jun 28;65(7):1243–1253. [PubMed]
  • Pepinsky RB. Selective precipitation of proteins from guanidine hydrochloride-containing solutions with ethanol. Anal Biochem. 1991 May 15;195(1):177–181. [PubMed]
  • Raychaudhuri P, Bagchi S, Devoto SH, Kraus VB, Moran E, Nevins JR. Domains of the adenovirus E1A protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes. Genes Dev. 1991 Jul;5(7):1200–1211. [PubMed]
  • Schöler HR, Ciesiolka T, Gruss P. A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell. 1991 Jul 26;66(2):291–304. [PubMed]
  • Simon MC, Rooney RJ, Fisch TM, Heintz N, Nevins JR. E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence. Proc Natl Acad Sci U S A. 1990 Jan;87(2):513–517. [PMC free article] [PubMed]
  • Vallee BL, Coleman JE, Auld DS. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):999–1003. [PMC free article] [PubMed]
  • Webster LC, Ricciardi RP. trans-dominant mutants of E1A provide genetic evidence that the zinc finger of the trans-activating domain binds a transcription factor. Mol Cell Biol. 1991 Sep;11(9):4287–4296. [PMC free article] [PubMed]
  • Webster N, Jin JR, Green S, Hollis M, Chambon P. The yeast UASG is a transcriptional enhancer in human HeLa cells in the presence of the GAL4 trans-activator. Cell. 1988 Jan 29;52(2):169–178. [PubMed]
  • Webster NJ, Green S, Tasset D, Ponglikitmongkol M, Chambon P. The transcriptional activation function located in the hormone-binding domain of the human oestrogen receptor is not encoded in a single exon. EMBO J. 1989 May;8(5):1441–1446. [PMC free article] [PubMed]
  • Whyte P, Williamson NM, Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 1989 Jan 13;56(1):67–75. [PubMed]
  • Winberg G, Shenk T. Dissection of overlapping functions within the adenovirus type 5 E1A gene. EMBO J. 1984 Aug;3(8):1907–1912. [PMC free article] [PubMed]
  • Wu L, Rosser DS, Schmidt MC, Berk A. A TATA box implicated in E1A transcriptional activation of a simple adenovirus 2 promoter. Nature. 1987 Apr 2;326(6112):512–515. [PubMed]
  • Yee SP, Branton PE. Analysis of multiple forms of human adenovirus type 5 E1A polypeptides using an anti-peptide antiserum specific for the amino terminus. Virology. 1985 Oct 30;146(2):315–322. [PubMed]
  • Zajchowski DA, Boeuf H, Kédinger C. The adenovirus-2 early EIIa transcription unit possesses two overlapping promoters with different sequence requirements for EIa-dependent stimulation. EMBO J. 1985 May;4(5):1293–1300. [PMC free article] [PubMed]
  • Zu YL, Maekawa T, Matsuda S, Ishii S. Complete putative metal finger and leucine zipper structures of CRE-BP1 are required for the E1A-induced trans-activation. J Biol Chem. 1991 Dec 15;266(35):24134–24139. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...