title: Yin Yang 1 regulates the transcriptional repression of Survivin.
abstract: The mechanisms for regulation of the Inhibitor of Apoptosis (IAP) Survivin in cells undergoing stress associated with tumor development and the tumor microenvironment are not well understood. The stress response transcription factors HIF-1α and Yin Yang 1 (YY1) were hypothesized to contribute to the upregulation of Survivin in tumor cells. As expected, U2OS cells overexpressing HIF-1α showed a 2- to 3-fold transactivation when transfected. Surprisingly, when YY1 was overexpressed in this survivin promoter reporter system, luciferase expression was repressed 30- to 40-fold. YY1 involvement in survivin promoter repression was confirmed using siRNA directed against YY1. These studies showed that knockdown of YY1 releases the survivin promoter from the observed repression and leads to a 3- to 5-fold increase in promoter activity above basal levels. A U2OS cell line containing a stable YY1 Tet-off system was used to determine whether a temporal increase in YY1 expression affects Survivin protein levels. A low to moderate decrease in Survivin protein was observed 24h and 48h after Tet removal. Studies also confirmed that YY1 is capable of directly binding to the survivin promoter. Collectively, these findings identify novel basal transcriptional requirements of survivin gene expression which are likely to play important roles in the development of cancer and resistance to its treatment.
authors: Center for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States; Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: ngalloway@llu.edu.
authors: Nicholas R
authors: NR
authors: Galloway
authors: Center for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States; Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: cdiazosterman@llu.edu.
authors: Carlos J
authors: CJ
authors: Diaz Osterman
authors: Center for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States; Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: kreiber@llu.edu.
authors: Karl
authors: K
authors: Reiber
authors: Center for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States; Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: jjutzy@llu.edu.
authors: Jessica M S
authors: JM
authors: Jutzy
authors: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: Fengzhi.Li@RoswellPark.org.
authors: Fengzhi
authors: F
authors: Li
authors: Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: gsui@wfubmc.edu.
authors: Guangchao
authors: G
authors: Sui
authors: Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: usoto@llu.edu.
authors: Ubaldo
authors: U
authors: Soto
authors: Center for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States; Department of Basic Sciences, Division of Biochemistry and Microbiology, Loma Linda University, Loma Linda, CA 92350, United States. Electronic address: nwall@llu.edu.
authors: Nathan R
authors: NR
authors: Wall
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D008156:Luciferases
keywords: HIF-1; IAP; Survivin; Transcriptional repressor; YY1