title: TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene.
abstract: Tumor suppressor p53 transcriptionally regulates hundreds of genes involved in various cellular functions. However, the detailed mechanisms underlying the selection of p53 targets in response to different stresses are still elusive. Here, we identify TFIIS.h, a transcription elongation factor, as a new transcriptional target of p53, and also show that it can enhance the efficiency of transcription elongation of apoptosis-associated bax gene, but not cell cycle-associated p21 (CDKN1A) gene. TFIIS.h is revealed as a p53 target through microarray analysis of RNAs extracted from cells treated with or without inauhzin (INZ), a p53 activator, and further confirmed by RT-q-PCR, western blot, luciferase reporter, and ChIP assays. Interestingly, knocking down TFIIS.h impairs, but overexpressing TFIIS.h promotes, induction of bax, but not other p53 targets including p21, by p53 activation. In addition, overexpression of TFIIS.h induces cell death in a bax- dependent fashion. These findings reveal a mechanism by which p53 utilizes TFIIS.h to selectively promote the transcriptional elongation of the bax gene, upsurging cell death in response to severe DNA damage.
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Liao
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.|Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Strong
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Shelya
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Pathology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Flemington
authors.affiliation: Department of Biochemistry &Molecular Biology and Cancer Center, Tulane University School of Medicine, 1430, Louisiana, LA 70112, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
mesh_terms: D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010640:Phenothiazines / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D007211:Indoles; D010640:Phenothiazines; C495901:TP53 protein, human; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C573921:inauzhin; C018648:transcription factor S-II