The Cdc25C phosphatase mediates cellular entry into mitosis. The cdc25C gene is a target for transcriptional downregulation by the tumor suppressor protein p53, and this repression can be shown to contribute to p53-dependent cell cycle arrest. Two independent mechanisms have been identified. One involves the direct binding of p53 to a site in the cdc25C promoter, and the second involves a CDE/CHR element. Both of these mediate p53-dependent repression at levels of p53 comparable to those produced by DNA damage. Three CCAAT elements in the cdc25C promoter that were previously implicated in p53-dependent repression fail to do so at physiologically relevant levels of p53. Repression of Cdc25C by p53 represents an additional mechanism for p53-dependent cell cycle arrest in response to DNA damage. Importantly, this is a clear demonstration of p53-mediated transcriptional downregulation that is dependent on sequence-specific DNA binding by p53.

Wild type p53 expressed from a temperature-sensitive (ts p53) construct induces both G1 cell cycle arrest and apoptosis in the p53-negative J3D mouse T lymphoma line (Wang et al., 1995). Using di erential display analysis, we have identi®ed one new p53-induced gene, wig-1 (for wild type p53-induced gene 1), whose 7.6 kb and 2.2 kb transcripts are upregulated in ts p53-transfected J3D cells following induction of wild type p53 expression by temperature shift to 328C. The wig-1 transcripts were also induced in irradiated NIH3T3 and p21 7/7 ®broblasts but not in irradiated p53 7/7 ®bro-blasts. Whole body gamma irradiation caused induction of both wig-1 transcripts in mouse brain, testis, kidney, spleen and lung. A basal wig-1 expression was detected in brain, testis and kidney. The WIG-1 protein contains three zinc ®nger motifs and a putative nuclear localization signal.

Summary Chromosome 6 deletions are common in human neoplasms including gliomas. In order to study the frequency and identify commonly deleted regions of chromosome 6 in astrocytomas, 159 tumours (106 glioblastomas, 39 anaplastic astrocytomas and 14 astrocytomas malignancy grade II) were analysed using 31 microsatellite markers that span the chromosome. Ninety-five per cent of cases with allelic losses had losses affecting 6q. Allelic losses were infrequent in astrocytomas malignancy grade II (14%) but more usual in anaplastic astrocytomas (38%) and glioblastomas (37%). Evidence for clonal heterogeneity in the astrocytomas and anaplastic astrocytomas was frequently observed (i.e. co-existence of subpopulations with and without chromosome 6 deletions). Clonal heterogeneity was less common in glioblastomas. Five commonly deleted regions were identified on 6q. These observations suggest that a number of tumour suppressor genes are located on 6q and that these genes may be involved in the progression of astrocytic tumours.