DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150 super(Sal2)

The product of the SALL2 protein p150 super(Sal2) is a multi-zinc finger transcription factor with growth arrest and proapoptotic functions that overlap those of p53. Its DNA-binding properties are unknown. We have used a modified SELEX procedure with purified p150 super(Sal2) and a pool of oligonucleotides of random sequence to identify those that are bound preferentially by p150 super(Sal2). The consensus sequence for optimal binding in vitro is van der (T/C)GGG, placing p150 super(Sal2) among a large group of GC box-binding proteins including the Sp1 family of transcription factors. A triple zinc finger motif in p150 super(Sal2) similar to that in Sp1 is required for DNA binding. p150 super(Sal2) and Sp1 show evidence of co-operative binding in vitro and of interaction in vivo. p150 super(Sal2), a known activator of the CDK inhibitor p21 super(Cip1/Waf1) (p21), binds to regions of the human p21 promoter that contain variations of the consensus sequence in multiple copies. p150 super(Sal2) is also shown to bind to the BAX promoter with similar elements and to activate its expression following an apoptotic stimulus. These results demonstrate binding of p150 super(Sal2) to two natural promoters with GC elements related to the optimal binding sequence defined in vitro and whose regulation is important for suppression of tumor growth. DNA-binding properties of p150 super(Sal2) have been defined in vitro and in vivo. p150 super(Sal2) binds to GC-rich elements in the p21 super(Cip1/Waf1) and BAX promoters. p150 super(Sal2) activates the BAX promoter following an apoptotic stimulus. These DNA-binding properties of p150 super(Sal2) underlie its tumor suppressor-like functions.