2-Aminopurine unravels a role for pRB in the regulation of gene expression by transforming growth factor β

Giuseppe Giannini, Lucia Di Marcotullio, Francesca Zazzeroni, Edoardo Alesse, Massimo Zani, Anne T'Ang, Vincenzo Sorrentino, Isabella Screpanti, Luigi Frati, Alberto Gulino

Research output: Contribution to journalArticle

Abstract

Transforming growth factor type β (TGFβ) is a pleiotropic factor that regulates different cellular activities including cell growth, differentiation, and extracellular matrix deposition. All the known effects of TGFβ appear to be mediated by its interaction with cell surface receptors that possess a serine/threonine kinase activity. However, the intracellular signals that follow receptor activation and lead to the different cellular responses to TGFβ are still largely unknown. On the basis of the different sensitivity to the protein kinase inhibitor 2-aminopurine and the phosphatase inhibitor okadaic acid, we identified two distinct pathways through which TGFβ activates a genomic response. Consistently, 2-aminopurine prevented and okadaic acid potentiated the induction of JE by TGFβ. The induction of PAI- 1 and junB was instead potentiated by 2-aminopurine, after a transient inhibition and was unaffected by okadaic acid. The superinducing effect of 2- aminopurine required the presence of a functional RB protein since it was abolished in SV40 large T antigen-transfected cells, absent in the BT549 and Saos-2 RB-defective cell lines, and restored in BT549 and Saos-2 cells after reintroduction of pRB. The effects of 2-aminopurine on the TGFβ inducible junB expression occur in all the cell lines examined suggesting that junB, and possibly other genes, can be regulated by TGFβ through a distinct pRB- dependent pathway.

Original languageEnglish
Pages (from-to)5313-5319
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number8
DOIs
Publication statusPublished - Feb 21 1997

ASJC Scopus subject areas

  • Biochemistry

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    Giannini, G., Di Marcotullio, L., Zazzeroni, F., Alesse, E., Zani, M., T'Ang, A., Sorrentino, V., Screpanti, I., Frati, L., & Gulino, A. (1997). 2-Aminopurine unravels a role for pRB in the regulation of gene expression by transforming growth factor β. Journal of Biological Chemistry, 272(8), 5313-5319. https://doi.org/10.1074/jbc.272.8.5313