Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen

Hye Yeon Kim, Byung-Yoon Ahn, Yunje Cho

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Inactivation of the retinoblastoma (Rb) tumor suppressor by Simian virus 40 (SV40) large T antigen is one of the central features of tumorigenesis induced by SV40. Both the N-terminal J domain and the LxCxE motif of large T antigen are required for inactivation of Rb. The crystal structure of the N-terminal region (residues 7-117) of SV40 large T antigen bound to the pocket domain of Rb reveals that large T antigen contains a four-helix bundle, and residues from helices α2 and α4 and from a loop containing the LxCxE motif participate in the interactions with Rb. The two central helices and a connecting loop in large T antigen have structural similarities with the J domains of the molecular chaperones DnaJ and HDJ-1, suggesting that large T antigen may use a chaperone mechanism for its biological function. However, there are significant differences between large T antigen and the molecular chaperones in other regions and these differences are likely to provide the specificity needed for large T antigen to inactivate Rb.

Original languageEnglish
Pages (from-to)295-304
Number of pages10
JournalEMBO Journal
Volume20
Issue number1-2
DOIs
Publication statusPublished - 2001 Jan 15

Fingerprint

Simian virus 40
Retinoblastoma
Viral Tumor Antigens
Viruses
Tumors
Neoplasms
Molecular Chaperones
Carcinogenesis
Crystal structure

Keywords

  • Chaperone mechanism
  • Rb tumor suppressor
  • SV40 large T antigen
  • Viral oncogene

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen. / Kim, Hye Yeon; Ahn, Byung-Yoon; Cho, Yunje.

In: EMBO Journal, Vol. 20, No. 1-2, 15.01.2001, p. 295-304.

Research output: Contribution to journalArticle

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