Sp1 and Sp3 regulate basal transcription of the survivin gene.
Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. In this study, we cloned and identified the proximal 269 bp promoter of survivin gene, which exhibited strong promoter activity in HeLa cells. The TATA-less, GC-rich promoter contains 7 putative binding sites for Sp1, two of which (one at position -148 to -153, the other at position -127 to -140) are essential in regulating basal survivin promoter activity. Not only Sp1 but also Sp3 can activate the survivin promoter, which were proven by EMSA, blocking Sp1 or Sp3 using RNAi or mithramycin treatment of HeLa cells, and overexpression of Sp1 or Sp3. Our results collectively suggest that Sp1 cooperates with Sp3 to regulate survivin promoter activity.
Xu
Rang
R
Research Center for Human Gene Therapy, Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhang
Ping
P
Huang
Jian
J
Ge
ShengFang
S
Lu
Jian
J
Qian
GuanXiang
G
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D008926:Plicamycin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000903:Antibiotics, Antineoplastic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D000077022:Survivin; D051705:Sp3 Transcription Factor; D008156:Luciferases; D008926:Plicamycin