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

Xin Liu, Ronen Marmorstein

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2711-2716
Number of pages6
JournalGenes and Development
Volume21
Issue number21
DOIs
StatePublished - Nov 1 2007

Fingerprint

Virus Inactivation
Retinoblastoma Protein
Oncogene Proteins
Adenoviridae
E2F Transcription Factors
Cyclin B
Transcriptional Activation
Neoplasms

Keywords

  • Adenovirus e1a
  • Prb/e1a complex
  • Retinoblastoma protein
  • Tumor suppressor
  • Viral oncoprotein

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor. / Liu, Xin; Marmorstein, Ronen.

In: Genes and Development, Vol. 21, No. 21, 01.11.2007, p. 2711-2716.

Research output: Contribution to journalArticle

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