scholarly journals Interaction of a Cyclin E Fragment with Ku70 Regulates Bax-Mediated Apoptosis

2007 ◽  
Vol 27 (9) ◽  
pp. 3511-3520 ◽  
Author(s):  
Suparna Mazumder ◽  
Dragos Plesca ◽  
Michael Kinter ◽  
Alexandru Almasan
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cyclin E ◽  
Critical Role ◽  
Genotoxic Stress ◽  
Cell Types ◽  
Tumor Cell Lines ◽  
Cdk2 Complex ◽  
Apoptotic Effect

ABSTRACT The cyclin E/Cdk2 complex plays an essential role in the G1/S cell cycle transition and DNA replication. Earlier we showed that in hematopoietic tumor cells, caspase-mediated cleavage of cyclin E generates p18-cyclin E, which is unable to interact with Cdk2 and therefore plays a role independent of the cell cycle. The expression of a cleavage-resistant cyclin E mutant greatly diminishes apoptosis, indicating the critical role of cyclin E cleavage. p18-cyclin E expression can induce apoptosis or sensitization to apoptotic stimuli in many cell types. Here we identify Ku70 as a specific p18-cyclin E-interacting partner. In hematopoietic tumor cell lines, the association of p18-cyclin E with Ku70 induces the dissociation of Bax from Ku70, followed by Bax activation. This mechanism of Bax activation leads to the amplification of the apoptosis signal in all tumor cell lines examined. N-terminal Ku70 deletion mutants are unable to bind to p18-cyclin E to regulate its apoptotic effect. p18-cyclin E-mediated amplification of apoptosis is dependent on Bax and Ku70 being greatly diminished in Ku70−/− and Bax−/− mouse embryo fibroblasts and in hematopoietic cells where Bax knockdown was achieved by short interfering RNA. The p18-cyclin E/Ku70 and Bax/Ku70 interactions provide a balance between apoptosis and the survival of cells exposed to genotoxic stress.

scholarly journals Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas.

1989 ◽  
Vol 9 (11) ◽  
pp. 4722-4730 ◽  
Author(s):  
A L Hiti ◽  
E Bogenmann ◽  
F Gonzales ◽  
P A Jones
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cell Types ◽  
Chain Gene ◽  
Tumor Cell Lines ◽  
Myosin Heavy Chain Gene ◽  
Mouse Muscle ◽  
Primary Explants ◽  
Rhabdomyosarcoma Cell ◽  
Multinucleated Myotubes

Several human rhabdomyosarcoma cell lines, cultured primary tumor explants, and biopsies of tumor and normal skeletal muscle tissue expressed a 2.0-kilobase transcript that hybridized to the mouse muscle determination gene MyoD1. This transcript was found in tumor cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines derived from other mesenchymal tumor cell types. Expression of the human homolog of MyoD1 therefore can define a tumor as a rhabdomyosarcoma. Transfection of the mouse MyoD1 gene into the human rhabdomyosarcoma cell line RD increased the ability of the tumor cells to differentiate into multinucleated myotubes and enhanced myosin heavy-chain gene expression but did not decrease tumorigenicity in nude mice.

scholarly journals Cathepsin B activity in human lung tumor cell lines: ultrastructural localization, pH sensitivity, and inhibitor status at the cellular level.

1994 ◽  
Vol 42 (7) ◽  
pp. 917-929 ◽  
Author(s):  
E Spiess ◽  
A Brüning ◽  
S Gack ◽  
B Ulbricht ◽  
H Spring ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Tumor Cell ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Cathepsin B ◽  
Lung Tumor ◽  
Cell Types ◽  
Cellular Level ◽  
Tumor Cell Lines

We investigated the appearance and activity of the cysteine proteinase cathepsin B and its physiological inhibitors, stefins A and B, at the cellular level in human tumor cell lines HS-24, derived from a primary lung tumor (squamous cell), and SB-3, derived from a metastasis (lung adenocarcinoma). In addition to cathepsin B, these tumor cells also expressed the immunologically and functionally related cathepsin L, but not cathepsin H. Stefin A was found in HS-24 but not in SB-3 cells; stefin B was found in both cell types. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized and quantified. Thus, the cellular cathepsin B kinetics for the synthetic substrates Z-Arg-Arg-4M beta NA and Z-Val-Lys-Lys-Arg-4M beta NA, its pH dependence and inhibition by E64, stefins A and B, and cystatin C could be determined. From these measurements it appeared that the enzyme exhibited different cleavage rates for these substrates in the different cell types, showed considerable cleavage activity at neutral pH, which was stable under these conditions for extended time periods, and was highly sensitive to the inhibitors E64 and cystatin C but was considerably less sensitive to stefins, particularly stefin A. By conventional light microscopy, confocal laser scanning microscopy, and electron microscopy the enzymatic activity was localized in lysosomes, as expected, but also in the endoplasmic reticulum, nuclear membrane, and plasma membrane. The endoplasmic reticulum is a site at which only pre-mature enzyme forms exist, which are usually not active. The appearance of enzymatic activity at the plasma membrane confirms earlier biochemical and immunofluorescence microscopic investigations. The different sites of localization within the cells make it likely that different forms of the enzyme are expressed simultaneously, which follow alternate ways of processing and sorting. Taken together, the results support an involvement of the enzyme under extracellular conditions in degradative processes.

Artificial Zinc(II) Complexes Regulate Cell Cycle and Apoptosis-Related Genes in Tumor Cell Lines

ChemBioChem ◽  
2007 ◽  
Vol 8 (3) ◽  
pp. 332-340 ◽  
Author(s):  
Jian Gao ◽  
Ya-Guang Liu ◽  
Yaqing Zhou ◽  
Linda M. Boxer ◽  
F. Ross Woolley ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines

Evaluation of Effect of Triterpenes and Limonoids on Cell Growth, Cell Cycle and Apoptosis in Human Tumor Cell Lines

2010 ◽  
Vol 10 (10) ◽  
pp. 769-776 ◽  
Author(s):  
Cristiane M. Cazal ◽  
Kantima Choosang ◽  
Vanessa Gisele P. Severino ◽  
Marcio S. Soares ◽  
Andre Lucio F. Sarria ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Ruthenium(II) complex containing cinnamic acid derivative inhibits cell cycle progression at G0/G1 and induces apoptosis in melanoma cells

2022 ◽  
Author(s):  
Amanda Negreti ◽  
Guilherme Álvaro Ferreira da Silva ◽  
Carolina G Pressete ◽  
Rafael Fonseca ◽  
Caio Cesar Candido ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Targeted Therapy ◽  
Skin Cancer ◽  
Tumor Cell ◽  
Cell Cycle Progression ◽  
Tumor Cell Lines ◽  
Cinnamic Acid Derivative ◽  
Cycle Progression ◽  
Apoptotic Effect ◽  
Malignant Tumor Cell

Melanoma is a highly aggressive skin cancer with limited targeted therapy arsenal. The Ruthenium-based complexes have shown interesting pro-apoptotic effect on malignant tumor cell lines. In this study three Ruthenium(II)...

scholarly journals Inheritance of gene density–related higher order chromatin arrangements in normal and tumor cell nuclei

2003 ◽  
Vol 162 (5) ◽  
pp. 809-820 ◽  
Author(s):  
Marion Cremer ◽  
Katrin Küpper ◽  
Babett Wagler ◽  
Leah Wizelman ◽  
Johann v. Hase ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Radial Distribution ◽  
Normal Cell ◽  
Cell Types ◽  
Higher Order ◽  
Gene Density ◽  
Tumor Cell Lines ◽  
Cell Nuclei ◽  
Significant Difference

A gene density–related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119–1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.

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