The retinoblastoma-related Rb2/p130 gene is an effector downstream of AP-2 during neural differentiation

Marco G. Paggi, Francesco Bonetto, Anna Severino, Alfonso Baldi, Tullio Battista, Federica Bucci, Armando Felsani, Daniela Lombardi, Antonio Giordano

Research output: Contribution to journalArticlepeer-review

Abstract

Rb2/p130, a member of the Retinoblastoma family of growth and tumour suppressor genes, is extensively implicated in the control of cell cycle and differentiation. The minimal promoter region of Rb2/p130 in T98G human glioblastoma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulatory protein that plays a crucial role in ectodermal differentiation. This KER1 site interacted in vitro with AP-2, and AP-2 overexpression increased Rb2/p130 transcription and translation. We also found that rat PC12 pheochromocytoma cells, when induced to differentiate by NGF, displayed an increase of AP-2 protein levels and of Rb2/p130 transcription and protein levels. AP-2-transfected PC12 cells displayed enhanced transcription and translation of Rb2/p130 and of the cdk inhibitor p21WAFI/CIPI, a gene known to be under the control of AP-2, but unable by itself to elicit PC12 differentiation. Overexpression of either AP-2 or Rb2/p130 elicited per se cell differentiation in the absence of NGF, while coexpression of AP-2B, a negative regulator of AP-2 transcriptional activity, inhibited only AP-2-induced differentiation. Altogether, these results indicate that Rb2/p130 is a critical effector of AP-2 in sustaining ectodermal differentiation.

Original languageEnglish
Pages (from-to)2570-2578
Number of pages9
JournalOncogene
Volume20
Issue number20
DOIs
Publication statusPublished - May 3 2001

Keywords

  • AP-2
  • Differentiation
  • NGF
  • PC12
  • Rb2/p130

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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