P53 INHIBITS RNA-POLYMERASE III-DIRECTED TRANSCRIPTION IN A PROMOTER-DEPENDENT MANNER

Wild-type p53 represses Alu template activity in vitro and in vivo. Ho wever, upstream activating sequence elements from both the 7SL RNA gen e and an Alu source gene relieve p53-mediated repression. p53 also rep resses the template activity of the U6 RNA gene both in vitro and in v ivo but has no effect on in vitro transcription of genes encoding 5S R NS 7SL RNA, adenovirus VAI RNA, and tRNA. The N-terminal activation do main of p53, which binds TATA-binding protein (TBP), is sufficient for repressing Alu transcription in vitro, and mutation of positions 22 a nd 23 in this region impairs p53-mediated repression of an Alu templat e both in vitro and in vivo. p53's N-terminal domain binds TFIIIB, pre sumably through its known interaction with TBP, and mutation of positi ons 22 and 23 interferes with TFIIIB binding. These results extend p53 's transcriptional role to RNA polymerase III-directed templates and i dentify an additional level of Alu transcriptional regulation.