ThewstGene Regulates Multiple Forms of Thymocyte Apoptosis

Potter, Mark D.; Bernstein, Alan; Lee, Jonathan M

doi:10.1006/cimm.1998.1346

Cited by 20 publications

(14 citation statements)

References 19 publications

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“…An increase in initiation factors will surely explain an increase in certain proteins that may be involved in cancer formation. A correlation between apoptosis and eEF1A was suggested when elevated apoptosis was observed in eEF1A-deficient mice [58,59]. This suggested EF1 to be an inhibitor of apoptosis when it is up-regulated.…”

Section: Factors In Protein Translationmentioning

confidence: 99%

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Fitzpatrick

You²,

Bemis³

et al. 2007

Proteomics Clinical Apps

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Platinum-based chemotherapy, such as cisplatin, is the primary treatment for ovarian cancer. However, drug resistance has become a major impediment to the successful treatment of ovarian cancer. To date, the molecular mechanisms of resistance to platinum-based chemotherapy remain unclear. In this study, we applied an LC/MS-based protein quantification method to examine the global protein expression of two pairs of ovarian cancer cell lines, A2780/A2780-CP (cisplatin-sensitive/cisplatin-resistant) and 2008/2008-C13*5.25 (cisplatin-sensitive/cisplatinresistant). We identified and quantified over 2000 proteins from these cell lines and 760 proteins showed significant expression changes with a false discovery rate of less than 5% between paired groups. Based on the results we obtained, we suggest several potential pathways that may be involved in cisplatin resistance in human ovarian cancer. This study provides not only a new proteomic platform for large-scale quantitative protein analysis, but also important information for discovery of potential biomarkers of cisplatin resistance in ovarian cancer. Furthermore, these results may be clinically relevant for diagnostics, prognostics, and therapeutic improvement for ovarian cancer treatment.

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Section: Factors In Protein Translationmentioning

confidence: 99%

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Fitzpatrick

You²,

Bemis³

et al. 2007

Proteomics Clinical Apps

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“…For example, one potential clue has been provided by the observation that thymocytes from mice homozygous for the autosomal recessive mutation Wasted (wst/wst) have increased sensitivity to corticosteroid-induced apoptosis. 13 It has been suggested that elevated thymocyte apoptosis may be a major contributor to the lymphoid dysfunction and ultimate death in wst/wst mice. Identification of the mutant gene and its function in mice with the Wasted phenotype may possibly reveal insight into genes critical for induction of apoptosis in thymocytes.…”

Section: Evidence For Involvement Of the Glucocorticoid Receptor Tranmentioning

confidence: 99%

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

2002

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Glucocorticosteroid hormones induce apoptosis in lymphocytes. Therefore, glucocorticoids are commonly used as immunosuppressive and chemotherapeutic agents. This review examines many facets of the process by which glucocorticoids induce apoptosis. This process is divided into three stages, an initiation stage that involves glucocorticoid receptor-mediated gene regulation, a decision stage that involves the counterbalancing influence of prosurvival and proapoptotic factors, and the execution stage which involves caspase and endonuclease activation. Many aspects of glucocorticoid-induced apoptosis, such as mitochondrial dysfunction and caspase activation, are important steps in virtually all forms of apoptosis. But the process glucocorticoid-induced apoptosis differs from other forms of apoptosis in terms of initiation at the transcriptional level and involvement of the multicatalytic proteasome and calcium. Moreover, the abundant opportunity for crosstalk between the glucocorticoid receptor and other signaling pathways increases the complexity of glucocorticoid-induced apoptosis and its regulation.

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“…Homozygous deletion of eEF1A2 occurs in the wasted mouse (7). These mice develop normally but suffer from neuromuscular abnormalities and immunodeficiency and die at approximately 1 month of age (35,36). Importantly, eEF1A2 is likely to be a human oncogene, it is highly expressed, and its gene is amplified in 30 to 60% of human tumors of the breast, ovary, and lung (2, 24, 24a, 25, 40).…”

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confidence: 99%

Eukaryotic Elongation Factor 1A2 Cooperates with Phosphatidylinositol-4 Kinase III β To Stimulate Production of Filopodia through Increased Phosphatidylinositol-4,5 Bisphosphate Generation

Jeganathan

Morrow

Amiri

et al. 2008

Molecular and Cellular Biology

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Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a transforming gene product that is highly expressed in human tumors of the ovary, lung, and breast. eEF1A2 also stimulates actin remodeling, and the expression of this factor is sufficient to induce the formation of filopodia, long cellular processes composed of bundles of parallel actin filaments. Here, we find that eEF1A2 stimulates formation of filopodia by increasing the cellular abundance of cytosolic and plasma membrane-bound phosphatidylinositol-4,5 bisphosphate [PI(4,5)P 2 ]. We have previously reported that the eEF1A2 protein binds and activates phosphatidylinositol-4 kinase III beta (PI4KIII␤), and we find that production of eEF1A2-dependent PI(4,5)P 2 and generation of filopodia require PI4KIII␤. Furthermore, PI4KIII␤ is itself capable of activating both the production of PI(4,5)P 2 and the creation of filopodia. We propose a model for extrusion of filopodia in which eEF1A2 activates PI4KIII␤, and activated PI4KIII␤ stimulates production of PI(4,5)P 2 and filopodia by increasing PI4P abundance. Our work suggests an important role for both eEF1A2 and PI4KIII␤ in the control of PI(4,5)P 2 signaling and actin remodeling.Filopodia are fingerlike projections from the plasma membrane that are the first cellular structures to reach new spaces during cell migration. Filopodia are composed of bundled actin filaments and actin-associated proteins (9, 13). Transmembrane receptors within filopodia respond to extracellular cues and guide directional movement toward chemoattractants (26). In addition, filopodia contain abundant adhesion molecules that regulate cellular attachment to growth substrates and cell-cell interactions (37). As such, filopodia regulate several key physiological processes, including cell migration, wound healing, and development. For example, filopodia are essential for neurogenesis in mice and for cell-cell adhesion during Drosophila melanogaster embryogenesis (9, 13).We have previously described a role for eukaryotic elongation factor 1 alpha 2 (eEF1A2) in the initiation and maintenance of filopodia (1). In several types of mammalian cells, eEF1A2 expression is sufficient to stimulate formation of filopodia (1). eEF1A2 is one of two members of the eEF1A family of proteins, eEF1A1 and eEF1A2. During the elongation phase of protein synthesis, GTP-bound eEF1A proteins interact with amino-acylated tRNA and recruit them to the ribosome (18). While eEF1A1 and eEF1A2 are believed to have equivalent roles in protein translation, their tissue-specific expression patterns are each markedly different. eEF1A1 is expressed ubiquitously, whereas eEF1A2 is detectably expressed only in normal tissues of mammalian heart, brain, and skeletal muscle (24a, 24b, 28). Homozygous deletion of eEF1A2 occurs in the wasted mouse (7). These mice develop normally but suffer from neuromuscular abnormalities and immunodeficiency and die at approximately 1 month of age (35,36). Importantly, eEF1A2 is likely to be a human oncogene, it is highly expressed, and its gene is...

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ThewstGene Regulates Multiple Forms of Thymocyte Apoptosis

Cited by 20 publications

References 19 publications

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

Eukaryotic Elongation Factor 1A2 Cooperates with Phosphatidylinositol-4 Kinase III β To Stimulate Production of Filopodia through Increased Phosphatidylinositol-4,5 Bisphosphate Generation

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