RACK1 Interacts with E1A and Rescues E1A-induced Yeast Growth Inhibition and Mammalian Cell Apoptosis

Nianli Sang, Anna Severino, Patrizia Russo, Alfonso Baldi, Antonio Giordano, Anna Maria Mileo, Marco G. Paggi, Antonio De Luca

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The adenoviral E1A proteins are able to promote proliferation and transformation, inhibit differentiation, induce apoptosis, and suppress tumor growth. The extreme N terminus and conserved region one of E1A, which are indispensable for transcriptional regulation and for binding to p300/CBP, TBP, and pCAF, play essential roles in these abilities. These observations strongly suggest an intrinsic link between E1A-mediated transcriptional regulation and other effects. In this report, we show that E1A inhibits the normal growth of Saccharomyces cerevisiae HF7c, and this inhibition also depends on the domains required for transcriptional regulation. We demonstrate that E1A associates with histone acetyltransferase activity and represses the transactivation activity of transcription factor in S. cerevisiae, suggesting that E1A may suppress the expression of genes required for normal growth. Based on yeast growth rescue, we present a genetic screening strategy that identified RACK1 as an E1A antagonizing factor. Expression of human RACK1 efficiently relieves E1A-mediated growth inhibition in HF7c and protects human tumor cells from E1A-induced apoptosis. Finally, we show that RACK1 decreases E1A-associated histone acetyltransferase activity in yeast and mammalian cells, and physically interacts with E1A. Our data demonstrate that RACK1 is a repressor of E1A, possibly by antagonizing the effects of E1A on host gene transcription.

Original languageEnglish
Pages (from-to)27026-27033
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number29
DOIs
Publication statusPublished - Jul 20 2001

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Yeast
Yeasts
Cells
Apoptosis
Histone Acetyltransferases
Growth
Saccharomyces cerevisiae
Tumors
Genes
Genetic Testing
Transcription
Transcriptional Activation
Neoplasms
Screening
Transcription Factors
Gene Expression
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

RACK1 Interacts with E1A and Rescues E1A-induced Yeast Growth Inhibition and Mammalian Cell Apoptosis. / Sang, Nianli; Severino, Anna; Russo, Patrizia; Baldi, Alfonso; Giordano, Antonio; Mileo, Anna Maria; Paggi, Marco G.; De Luca, Antonio.

In: Journal of Biological Chemistry, Vol. 276, No. 29, 20.07.2001, p. 27026-27033.

Research output: Contribution to journalArticle

Sang, Nianli ; Severino, Anna ; Russo, Patrizia ; Baldi, Alfonso ; Giordano, Antonio ; Mileo, Anna Maria ; Paggi, Marco G. ; De Luca, Antonio. / RACK1 Interacts with E1A and Rescues E1A-induced Yeast Growth Inhibition and Mammalian Cell Apoptosis. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 29. pp. 27026-27033.
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