Ec. Thornborrow et Jj. Manfredi, The tumor suppressor protein p53 requires a cofactor to activate transcriptionally the human BAX promoter, J BIOL CHEM, 276(19), 2001, pp. 15598-15608
An important regulator of the proapoptotic BAX is the tumor suppressor prot
ein p53. Unlike the p21 gene, in which p53-dependent transcriptional activa
tion is mediated by a response element containing two consensus p53 half-si
tes, it previously was reported that activation of the BAX element by p53 r
equires additional sequences. Here, it is demonstrated that the minimal BAX
response element capable of mediating p53-dependent transcriptional activa
tion consists of two p53 half-sites plus an adjacent 6 base pairs (5'-GGGCG
T-3'). This GC-rich region constitutes a "GC box" capable both of binding m
embers of the Sp family of transcription factors, including Sp1 in vitro, a
nd of conferring Sp1-dependent transcriptional activation on a minimal prom
oter in cells. Mutations within this GC box abrogated the ability of p53 to
activate transcription without affecting the affinity of p53 for its bindi
ng site, demonstrating that these 6 bases are required for p53-dependent ac
tivation. In addition, a positive correlation was observed between the abil
ity of p53 to activate transcription in cells and the ability of Sp1 to bin
d this response element in vitro. Mutations that inhibited Sp1 binding also
blocked the ability of p53 to activate transcription through this element.
Together, these results suggest a model in which p53 requires the cooperat
ion of Sp1 or a Sp1-like factor to mediate transcriptional activation of th
e human BAX promoter.