TRANSCRIPTIONAL REGULATION BY P53 - FUNCTIONAL INTERACTIONS AMONG MULTIPLE REGULATORY DOMAINS

The tumor suppressor p53 protein possesses activities typical of eukar yotic transcriptional activators; p53 binds to specific DNA sequences and stimulates transcription of the target genes. By a series of delet ion and domain-swapping studies, we report here that (i) p53 has two a uxiliary domains, which have little effect on the DNA binding activity of its core domain but are capable of modulating its transactivation activity in a target site dependent manner; (ii) p53 contains two cell -specific transcriptional inhibitory domains, I1 and I2, which are act ive in Saos-2 and HeLa cells but not in HepG2 and Hep3B cells; and (ii i) I1 inhibits the activity of several structurally different activati ng regions. These results demonstrate that the apparent transcrip tion al activity of p53 is determined by collaborations among its regulator y domains, its target sites, and the cellular environment.