Vaccinia virus-mediated cell cycle alteration involves inactivation of tumour suppressors associated with Brf1 and TBP

Na Kyung Yoo, Chul Woong Pyo, Youngho Kim, Byung-Yoon Ahn, Sang-Yun Choi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The vaccinia virus (VV) replicates robustly and alters the progression of the cell cycle via an unknown mechanism. Herein, we provide evidence for the existence of a unique VV infection-induced cell cycle control mechanism. The regulation is correlated with the inactivation of p53 and Rb, which are associated with the RNA polymerase III transcription factor B (TFIIIB) subunits, TBP and Brf1 respectively. VV infection induced the expression of Mdm2 and its translocation into the nucleus, thereby resulting in a disruption of p53. VV also stimulated the expression of TFIIIB and TFIIIC, and consequently induced tRNA synthesis. On the other hand, the total level of Rb was not significantly influenced, but the level of hypo-phosphorylated Rb was enhanced, partially due to the VV-induced downregulation of cyclin-dependent kinases 4 and 6. However, the hypo-phosphorylated Rb appeared to be largely sequestered into a complex with Brf1, which resulted in the blockage of Rb function to repress E2F1 transactivation, thereby leading to a moderately higher proportion of cells in the S and G2 phases. Conversely, the enforced expression of exogenous Rb restored the normally observed cell cycle patterns. Overall, these controls may contribute to the efficient replication of the virus in rapidly growing cells.

Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalCellular Microbiology
Volume10
Issue number3
DOIs
Publication statusPublished - 2008 Mar 1

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Vaccinia virus
Viruses
Tumors
Cell Cycle
Cells
Transcription Factor TFIIIB
Virus Diseases
Neoplasms
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
RNA Polymerase III
G2 Phase
Virus Replication
Transfer RNA
Cell Cycle Checkpoints
S Phase
Transcriptional Activation
Down-Regulation
tributyl phosphate
Transcription Factors

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Vaccinia virus-mediated cell cycle alteration involves inactivation of tumour suppressors associated with Brf1 and TBP. / Yoo, Na Kyung; Pyo, Chul Woong; Kim, Youngho; Ahn, Byung-Yoon; Choi, Sang-Yun.

In: Cellular Microbiology, Vol. 10, No. 3, 01.03.2008, p. 583-592.

Research output: Contribution to journalArticle

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