THE CANDIDATE TUMOR-SUPPRESSOR P33(ING1) COOPERATES WITH P53 IN CELL-GROWTH CONTROL

The candidate tumour-suppressor gene ING1 has been identified by using the genetic suppressor element (GSE) methodology(1). ING1 encodes a n uclear protein, p33(ING1), overexpression of which inhibits growth of different cell lines. The properties of p33(ING1) suggest its involvem ent in the negative regulation of cell proliferation and in the contro l of cellular ageing, anchorage dependence and apoptosis(1-3). These c ellular functions depend largely on the activity of p53, a tumour-supp ressor gene that determines the cellular response to various types of stress(4). Here we report that the biological effects of ING1 and p53 are interrelated and require the activity of both genes: neither of th e two genes can, on its own, cause growth inhibition when the other on e is suppressed. Furthermore, activation of transcription from the P21 /WAF1 promoter, a key mechanism of p53-mediated growth control, depend s on the expression of ING1. A physical association between p33(ING1) and p53 proteins has been detected by immunoprecipitation. These resul ts indicate that p33(ING1) is a component of the p53 signalling pathwa y that cooperates with p53 in the negative regulation of cell prolifer ation by modulating p53-dependent transcriptional activation.