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Literature DB >> 17974914

Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.

Abstract

The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.

Entities: Disease Gene

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Year: 2007 PMID： 17974914 PMCID： PMC2045126 DOI： 10.1101/gad.1590607

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

32 in total

1. Adenovirus E1A makes two distinct contacts with the retinoblastoma protein.

Authors: N Dyson; P Guida; C McCall; E Harlow
Journal: J Virol Date: 1992-07 Impact factor: 5.103

2. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F.

Authors: K Helin; J A Lees; M Vidal; N Dyson; E Harlow; A Fattaey
Journal: Cell Date: 1992-07-24 Impact factor: 41.582

3. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein.

Authors: M E Ewen; Y G Xing; J B Lawrence; D M Livingston
Journal: Cell Date: 1991-09-20 Impact factor: 41.582

4. Identification of distinct roles for separate E1A domains in disruption of E2F complexes.

Authors: M A Ikeda; J R Nevins
Journal: Mol Cell Biol Date: 1993-11 Impact factor: 4.272

5. Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth.

Authors: H G Wang; Y Rikitake; M C Carter; P Yaciuk; S E Abraham; B Zerler; E Moran
Journal: J Virol Date: 1993-01 Impact factor: 5.103

6. Identification of discrete structural domains in the retinoblastoma protein. Amino-terminal domain is required for its oligomerization.

Authors: C E Hensey; F Hong; T Durfee; Y W Qian; E Y Lee; W H Lee
Journal: J Biol Chem Date: 1994-01-14 Impact factor: 5.157

7. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes.

Authors: A R Fattaey; E Harlow; K Helin
Journal: Mol Cell Biol Date: 1993-12 Impact factor: 4.272

8. The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E.

Authors: Y Li; C Graham; S Lacy; A M Duncan; P Whyte
Journal: Genes Dev Date: 1993-12 Impact factor: 11.361

9. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.

Authors: Z Arany; D Newsome; E Oldread; D M Livingston; R Eckner
Journal: Nature Date: 1995-03-02 Impact factor: 49.962

10. Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters.

Authors: H K Wong; E B Ziff
Journal: J Virol Date: 1994-08 Impact factor: 5.103

39 in total

1. Crystal structure of the unliganded retinoblastoma protein pocket domain.

Authors: Eva Rose M Balog; Jason R Burke; Greg L Hura; Seth M Rubin
Journal: Proteins Date: 2011-04-12

2. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption.

Authors: L A Seifried; S Talluri; M Cecchini; L M Julian; J S Mymryk; F A Dick
Journal: J Virol Date: 2008-02-27 Impact factor: 5.103

3. The interaction between an acidic transcriptional activator and its inhibitor. The molecular basis of Gal4p recognition by Gal80p.

Authors: James B Thoden; Louise A Ryan; Richard J Reece; Hazel M Holden
Journal: J Biol Chem Date: 2008-08-13 Impact factor: 5.157

Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.

1. Adenovirus E1A makes two distinct contacts with the retinoblastoma protein.

2. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F.

3. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein.

4. Identification of distinct roles for separate E1A domains in disruption of E2F complexes.

5. Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth.

6. Identification of discrete structural domains in the retinoblastoma protein. Amino-terminal domain is required for its oligomerization.

7. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes.

8. The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E.

9. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.

10. Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters.

1. Crystal structure of the unliganded retinoblastoma protein pocket domain.

2. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption.

3. The interaction between an acidic transcriptional activator and its inhibitor. The molecular basis of Gal4p recognition by Gal80p.

4. Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control.

5. Adenovirus E1A oncogene induces rereplication of cellular DNA and alters DNA replication dynamics.

6. Structural and functional characterization of the acidic region from the RIZ tumor suppressor.

Review 7. Intrinsic structural disorder in adenovirus E1A: a viral molecular hub linking multiple diverse processes.

8. Expanding the proteome: disordered and alternatively folded proteins.

9. Mapping the interactions of adenoviral E1A proteins with the p160 nuclear receptor coactivator binding domain of CBP.

Review 10. Viral manipulation of the host epigenome for oncogenic transformation.