A novel mutation lacking the bromodomain of the transcriptional coactivator p300 in the SiHa cervical carcinoma cell line.

The transcriptional coactivator p300, a histone acetyltransferase (HAT), plays key roles in the regulation of cell proliferation and differentiation. p300 is targeted by viral oncoproteins, and mutations of p300, accompanied by inactivation of the second allele, have been reported in certain types of cancers originating in the epithelium. Here, we identified a homozygous p300 deletion of exons 15--18 in the SiHa cervical carcinoma cell line, which results in an in-frame deletion that causes specific loss of the bromodomain, a conserved domain implicated in the regulation of HAT activity. Furthermore, we show that the mutation severely impaired its ability to activate the p21(WAF1/CIP1) promoter in transient reporter assay. These results suggest a critical role for the bromodomain in p300 functions as a tumor-suppressor gene. Copyright 2001 Academic Press.