title: DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(Sal2).
abstract: The product of the SALL2 protein p150(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(Sal2) and a pool of oligonucleotides of random sequence to identify those that are bound preferentially by p150(Sal2). The consensus sequence for optimal binding in vitro is GGG(T/C)GGG, placing p150(Sal2) among a large group of GC box-binding proteins including the Sp1 family of transcription factors. A triple zinc finger motif in p150(Sal2) similar to that in Sp1 is required for DNA binding. p150(Sal2) and Sp1 show evidence of co-operative binding in vitro and of interaction in vivo. p150(Sal2), a known activator of the CDK inhibitor p21(Cip1/Waf1) (p21), binds to regions of the human p21 promoter that contain variations of the consensus sequence in multiple copies. p150(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(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.
authors.affiliation: Department of pathology NRB-939, Harvard Medical School, 77 Avenue Pasteur, Boston, MA 02115, USA.
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Chang K
authors.initials: CK
authors.lastname: Sung
authors.forename: Hyungshin
authors.initials: H
authors.lastname: Yim
authors.forename: Philip
authors.initials: P
authors.lastname: Troke
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D052156:SELEX Aptamer Technique; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; C104147:SALL2 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D004247:DNA; D005982:Glutathione Transferase