Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance.

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Abstract Text:

Jianguo Wu,Pasha Apontes,Lei Song,Ping Liang,Lily Yang,Fengzhi Li,

We have previously shown that hedamycin, a GC-rich DNA-binding antitumor agent, downregulates survivin transcription (Wu et al. (2005) Molecular mechanism of inhibition of survivin transcription by the GC-rich sequence selective DNA-binding antitumor agent, hedamycin: evidence of survivin downregulation associated with drug sensitivity. J. Biol. Chem., 280, 9745-9751). Here, we report that treatment of cancer cells with Hoechst33342, an AT-rich DNA-binding ligand, upregulated survivin protein, mRNA and promoter activity. Functional analysis of survivin promoter-luciferase constructs followed by in vivo footprinting experiments identified a 28-bp AT-rich DNA element (-908 to -881, designated as H369W) that mediates a major effect of Hoechst33342 on the upregulation of survivin promoter activity. Electrophoresis mobility shift assay (EMSA) experiments showed that Hoechst33342 binds to H369W and abrogates H369W-protein interactions. Intriguingly, there is a highly conserved DNA-binding motif for growth factor independence 1 (Gfi-1), a transcriptional repressor protein, in the H369W DNA element. Accordingly, EMSA experiments demonstrated that either the cold canonical Gfi-1-binding DNA oligonucleotide or the cold H369W specifically competes with H369W-protein complexes. Consistently, anti-Gfi-1 antibody is able to supershift the H369W-protein complex on the EMSA gel. Lastly, our data reveal that upregulation of survivin by Hoechst33342 is involved in cancer drug resistance. We propose that hindrance of H369W-Gfi-1 interactions in the survivin promoter, initiated by Hoechst33342, contributes to upregulation of survivin transcription, and as a consequence, hampers Hoechst33342's cytotoxicity.

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Publishing Authors By Initials

J Wu,P Apontes,L Song,P Liang,L Yang,F Li,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

PUBMED ID PMID:

MEDLINE DATE:

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nucleic acids research

VOLUME: 35

Page Numbers: 2390-402

Journal Abbreviation:

ISSN: 1362-4962

DAY: 28

MONTH: 03

YEAR: 2007

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 411011

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: biosynthesis

Chemical & Substance for Abstract: Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance. Information

Substance Name: Luciferases

Registry Number: EC 1.13.12.-

Grant and Affiliation Information for Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance.

AFFILIATION: Department of Pharmacology, Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Country: England

AGENCY: United States NCI

GRANT: CA16056

ACRONYM: CA

MEDLINETA: Nucleic Acids Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding ligand, Hoechst33342: evidence for survivin involvement in drug resistance Related Publications

• Airway epithelium and mucus: intracellular signaling pathways for gene expression and secretion.
• Imaging diagnosis of enlarged superior ophthalmic vein.
• Lung autotransplantation technique for treating central lung cancer of upper lobe.
• Study on the relationship between opioid receptors and fetal distress.
• The clinical value of rearrangement of IgH gene and bcl-2/J(H) fuse gene in the diagnosis of orbital lymphoproliferative disorders.
• The effect of metal copper on fracture healing in chicken.
• Transforming growth factor-beta -Smad signaling pathway cooperates with NF-kappa B to mediate nontypeable Haemophilus influenzae-induced MUC2 mucin transcription.
• [Advances in research on ion-channel gating mechanism]
• [Association of dendritic cell infiltration with prognosis and lymph node metastasis of renal cell carcinoma]
• [Changes in serum concentration of podophyllotoxin after its topical application with liposome on rat skin]
• [ECG signal compression based on best basis of wavelet packets]
• [Effect of lovastatin on proliferation and extracellular matrix secretion of rat hepatic stellate cells in vitro]
• [Effects of hypoxic exposure on coordinative expression of cytochrome oxidase subunits I and IV in rat cerebral cortex]
• [Effects of nitric oxide on pleural lymphatic stomata and lymphatic drainage in the rat]
• [Evaluation of p53, p21waf1, and PCNA in the diagnosis on lung cancer]
• [Evaluation the pathological diagnostic values of koilocyte in condyloma acuminatum]
• [Gap junctions in the nervous tissue]
• [Genotyping of HIV resistant alleles in indigenous Tibetan ethnic group of China: low frequency of CCR5triangle32 and high frequency of CCR2b-64I alleles]
• [Logistic regression analysis of wedge-shaped defects in the middle-aged and elderly]
• [Molecular genetic basis of Gilbert's syndrome]
• [Observation on the effect of disinfection to HBsAg by electrolyzed oxidizing water]
• [P2X purinoceptors and their regulations]
• [Preparation of rhBMP-2/BCB reconstituted bone xenograft and assay of its osteoinductivity]
• [Selective transmission of hepatitis B virus variant with S gene mutation between HBV-carrier mothers and their infants]
• [Surgical repair of postinfarction ventricular septal rupture]
• [Surgical treatment of anomalous origin of the left coronary artery from the pulmonary artery]
• [The correlations between plasma TNF-alpha, NO, NOS levels and brain lateralization in mice]
• [The genotype analysis of glucose-6-phosphate dehydrogenase deficiency in Yunnan province]
• [The relationship of low density lipoprotein receptor gene polymorphism and hyperlipidemia]
• [Umbilical cord blood transplantation (UCBT) in thalassemia children]