BAG3 controls angiogenesis through regulation of ERK phosphorylation

A. Falco, M. Festa, A. Basile, A. Rosati, M. Pascale, F. Florenzano, S. L. Nori, V. Nicolin, M. Di Benedetto, M. L. Vecchione, C. Arra, A. Barbieri, V. De Laurenzi, M. C. Turco

Research output: Contribution to journalArticle

Abstract

BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an anti-apoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase.

Original languageEnglish
Pages (from-to)5153-5161
Number of pages9
JournalOncogene
Volume31
Issue number50
DOIs
Publication statusPublished - Dec 13 2012

Keywords

  • angiogenesis
  • BAG3
  • tumour

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Falco, A., Festa, M., Basile, A., Rosati, A., Pascale, M., Florenzano, F., Nori, S. L., Nicolin, V., Di Benedetto, M., Vecchione, M. L., Arra, C., Barbieri, A., De Laurenzi, V., & Turco, M. C. (2012). BAG3 controls angiogenesis through regulation of ERK phosphorylation. Oncogene, 31(50), 5153-5161. https://doi.org/10.1038/onc.2012.17