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Keywords
(7)
Binding Protein
Dna Binding
Random Sequence
Transcription Factor
Tumor Growth
Tumor Suppressor
Zinc Finger
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DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150 Sal2
DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150 Sal2,10.1016/j.bbagrm.2011.02.002,Biochimica Et B
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DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150 Sal2
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Hongcang Gu
,
Dawei Li
,
Chang K. Sung
,
Hyungshin Yim
,
Philip Troke
,
Thomas Benjamin
The product of the SALL2 protein p150Sal2 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 p150Sal2 and a pool of oligonucleotides of
random sequence
to identify those that are bound preferentially by p150Sal2. The consensus sequence for optimal binding in vitro is GGG(T/C)GGG, placing p150Sal2 among a large group of GC box-binding proteins including the Sp1 family of transcription factors. A triple
zinc finger
motif in p150Sal2 similar to that in Sp1 is required for DNA binding. p150Sal2 and Sp1 show evidence of co-operative binding in vitro and of interaction in vivo. p150Sal2, a known activator of the CDK inhibitor p21Cip1/Waf1 (p21), binds to regions of the human p21 promoter that contain variations of the consensus sequence in multiple copies. p150Sal2 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 p150Sal2 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.
Journal:
Biochimica Et Biophysica Acta-gene Regulatory Mechanisms - BBA-GENE REGUL MECH
, vol. 1809, no. 4, pp. 276-283, 2011
DOI:
10.1016/j.bbagrm.2011.02.002
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