scholarly journals Enhanced Expression of Apoptin by the Myc–Max Binding Motif and SV40 Enhancer for SCLC Gene Therapy

2005 ◽  
Vol 69 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Joon-Seok SONG
Keyword(s):  
Gene Therapy ◽  
Binding Motif ◽  
Sv40 Enhancer ◽  
Enhanced Expression

Non-oncogenic deletion mutants of adenoviral E1A enhance paclitaxel induced apoptosis of ovarian cancer cells

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14102-14102
Author(s):  
C. Kurzeder ◽  
C. Hanselmann ◽  
N. DeGregorio ◽  
G. Sauer ◽  
B. Opalka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Therapy ◽  
Ovarian Carcinoma ◽  
Cancer Cells ◽  
Expression System ◽  
Substantial Reduction ◽  
Ovarian Cancer Cells ◽  
Binding Motif ◽  
Therapeutic Effects ◽  
Induced Apoptosis

14102 Background: The phenotypical characteristics and spread of ovarian cancer cells, suggest intraperitoneal gene therapy of this disease. Phase I trials have been conducted to investigate the potential clinical benefits of adenoviral E1A-based gene therapy. Further gene therapeutic approaches which aim to enhance the efficacy of E1A-induced apoptosis in a multimodal approach including conventional chemotherapy are planned. However, besides tumor-suppressive effects, E1A is also known to transform rodent cells in conjunction with other factors, e.g. an activated ras oncogene. In an effort to eliminate elements favouring malignant conversion, the potential therapeutic effect of the E1AdelCR2 deletion mutant on ovarian cancer cells was studied. Methods: To avoid any selection bias, a doxycyclin-regulated system was used to express E1A wildtype protein and the mutant E1AdelCR2 lacking the p105RB-binding motif. The effects of the E1A proteins on proliferation and induction of apoptosis in ovarian carcinoma cell lines was studied with a WST-1 assay and fluorcytometric analysis of FITC labelled AnnexinV. Results: As confirmed by Western blot analyses, expression of the mutant proteins was almost completely suppressed in the presence of doxycyclin. Substantial reduction in proliferation was achieved by expression of both wildtype E1A and E1AdelCR2. Expression of E1AdelCR2 was sufficient by itself to induce apoptosis in 8,7% of ovarian carcinoma cells as shown by an increase of the fraction of Annexin binding OVMZ-8 cells. A strong synergistic effect with an increase of the fraction of apoptotoc cells by 16.7% was found when the cells were treated with paclitaxel. Conclusion: Deletion of the CR2 sequence should increase the safety of therapeutic applications of E1A without affecting tumor suppression. A doxycyclin-regulated expression system was established allowing the elucidation of the mechanisms underlying the therapeutic effects of E1A in ovarian cancer cells in the future by means of expression profiling and quantification of activated components of signal transduction pathways. No significant financial relationships to disclose.

scholarly journals Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif

2001 ◽  
Vol 91 (6) ◽  
pp. 851-856 ◽  
Author(s):  
Kazumi Nishino ◽  
Tadashi Osaki ◽  
Toru Kumagai ◽  
Takashi Kijima ◽  
Isao Tachibana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Binding Motif ◽  
Small Cell Lung

SAC3B is a target of CML19, the centrin 2 of Arabidopsis thaliana

2020 ◽  
Vol 477 (1) ◽  
pp. 173-189 ◽  
Author(s):  
Marco Pedretti ◽  
Carolina Conter ◽  
Paola Dominici ◽  
Alessandra Astegno
Keyword(s):  
Excision Repair ◽  
Complex Structure ◽  
Binding Motif ◽  
C Terminus ◽  
Repair Protein ◽  
Nucleotide Excision ◽  
Ef Hand ◽  
Molecular Determinants ◽  
Structure In Solution

Arabidopsis centrin 2, also known as calmodulin-like protein 19 (CML19), is a member of the EF-hand superfamily of calcium (Ca2+)-binding proteins. In addition to the notion that CML19 interacts with the nucleotide excision repair protein RAD4, CML19 was suggested to be a component of the transcription export complex 2 (TREX-2) by interacting with SAC3B. However, the molecular determinants of this interaction have remained largely unknown. Herein, we identified a CML19-binding site within the C-terminus of SAC3B and characterized the binding properties of the corresponding 26-residue peptide (SAC3Bp), which exhibits the hydrophobic triad centrin-binding motif in a reversed orientation (I8W4W1). Using a combination of spectroscopic and calorimetric experiments, we shed light on the SAC3Bp–CML19 complex structure in solution. We demonstrated that the peptide interacts not only with Ca2+-saturated CML19, but also with apo-CML19 to form a protein–peptide complex with a 1 : 1 stoichiometry. Both interactions involve hydrophobic and electrostatic contributions and include the burial of Trp residues of SAC3Bp. However, the peptide likely assumes different conformations upon binding to apo-CML19 or Ca2+-CML19. Importantly, the peptide dramatically increases the affinity for Ca2+ of CML19, especially of the C-lobe, suggesting that in vivo the protein would be Ca2+-saturated and bound to SAC3B even at resting Ca2+-levels. Our results, providing direct evidence that Arabidopsis SAC3B is a CML19 target and proposing that CML19 can bind to SAC3B through its C-lobe independent of a Ca2+ stimulus, support a functional role for these proteins in TREX-2 complex and mRNA export.

Antiangiogenic gene therapy delays growth of murine and human pancreatic adenocarcinoma in mice

2001 ◽  
Vol 120 (5) ◽  
pp. A349-A349
Author(s):  
J TSENG ◽  
F FARNEBO ◽  
O KISKER ◽  
C BECKER ◽  
C KUO ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Human Pancreatic Adenocarcinoma

Enhanced expression of TGFβ, collagen, and TIMP-1 genes in esophageal stricture

2001 ◽  
Vol 120 (5) ◽  
pp. A153-A153
Author(s):  
M KLINE ◽  
Z ZANG ◽  
K PATEL ◽  
S FRENCH ◽  
H TSUKAMOTO
Keyword(s):  
Esophageal Stricture ◽  
Enhanced Expression
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