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

Rb2/p130, a member of the Retinoblastoma family of growth and tumour suppre ssor genes, is extensively implicated in the control of cell cycle and diff erentiation. The minimal promoter region of Rb2/p130 in T98G human glioblas toma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulato ry protein that plays a crucial role in ectodermal differentiation, This KE R1 site interacted in vitro with AP-2, and AP-2 overexpression increased Rb 2/p130 transcription and translation, We also found that rat PC12 pheochrom ocytoma 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 p21(WAF1/CIP1), a gene known to be und er 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 differenti ation in the absence of NGF, while coexpression of AP-IB, a negative regula tor of AP-2 transcriptional activity, inhibited only AP-2-induced different iation, Altogether, these results indicate that Rb2/p130 is a critical effe ctor of AP-2 in sustaining ectodermal differentiation.