Live and let die: regulatory mechanisms in Fas-mediated apoptosis

Curtin, James F.; Cotter, Thomas G.

doi:10.1016/s0898-6568(03)00093-7

Cited by 170 publications

(155 citation statements)

References 147 publications

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“…It is possible that this difference is cell line specific, or is influenced by the expression of recombinant proteins. For instance, the CHO IFN-c cell line in the study by Wong et al produces a recombinant human interferon gamma, which has been documented to activate Fas death receptor signaling (Curtin and Cotter 2003;Ossina et al 1997;Spanaus et al 1998). Therefore, the observed transcriptional changes in the CHO IFNc batch culture might not be universally applicable to other CHO cell lines.…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

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The degradation of environmental conditions, such as nutrient depletion and accumulation of toxic waste products over time, often lead to premature apoptotic cell death in mammalian cell cultures and suboptimal protein yield. Although apoptosis has been extensively researched, the changes in the whole cell proteome during prolonged cultivation, where apoptosis is a major mode of cell death, have not been examined. To our knowledge, the work presented here is the first whole cell proteome analysis of non-induced apoptosis in mammalian cells. Flow cytometry analyses of various activated caspases demonstrated the onset of apoptosis in Chinese hamster ovary cells during prolonged cultivation was primarily through the intrinsic pathway. Differential in gel electrophoresis proteomic study comparing protein samples collected during cultivation resulted in the identification of 40 differentially expressed proteins, including four cytoskeletal proteins, ten chaperone and folding proteins, seven metabolic enzymes and seven other proteins of varied functions. The induction of seven ER chaperones and foldases is a solid indication of the onset of the unfolded protein response, which is triggered by cellular and ER stresses, many of which occur during prolonged batch cultures. In addition, the upregulation of six glycolytic enzymes and another metabolic protein emphasizes that a change in the energy metabolism likely occurred as culture conditions degraded and apoptosis advanced. By identifying the intracellular changes during cultivation, this study provides a foundation for optimizing cell line-specific cultivation processes, prolonging longevity and maximizing protein production.

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Section: Discussionmentioning

confidence: 99%

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

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“…Similarly to FLIP, the caspsase-8 L splice variant has a functional DED but lacks key residues in the catalytic domain, which allows it to interact with the DISC at the plasma membrane without being able to induce downstream caspase activation (Curtin and Cotter 2003). Thus, caspase-8 L behaves like c-FLIP and acts like a caspase-8 inhibitor (Himeji et al 2002).…”

Section: Transcriptional Regulation Of Caspasesmentioning

confidence: 99%

“…Thus, caspase-8 L behaves like c-FLIP and acts like a caspase-8 inhibitor (Himeji et al 2002). Methylation of the caspase-8 gene is thought to suppress caspase-8 expression in a variety of tumors Curtin and Cotter 2003). Pediatric tumors, including rhabdomyosarcomas, medulloblastomas, retinoblastomas, and neuroblastomas, have all been reported to exhibit methylation of the caspase-8 gene, correlating with a decrease in caspase-8 expression.…”

Section: Transcriptional Regulation Of Caspasesmentioning

confidence: 99%

Cellular Mechanisms Controlling Caspase Activation and Function

Parrish

Freel

Kornbluth

2013

Cold Spring Harbor Perspectives in Biology

491

367

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Caspases are the primary drivers of apoptotic cell death, cleaving cellular proteins that are critical for dismantling the dying cell. Initially translated as inactive zymogenic precursors, caspases are activated in response to a variety of cell death stimuli. In addition to factors required for their direct activation (e.g., dimerizing adaptor proteins in the case of initiator caspases that lie at the apex of apoptotic signaling cascades), caspases are regulated by a variety of cellular factors in a myriad of physiological and pathological settings. For example, caspases may be modified posttranslationally (e.g., by phosphorylation or ubiquitylation) or through interaction of modulatory factors with either the zymogenic or active form of a caspase, altering its activation and/or activity. These regulatory events may inhibit or enhance enzymatic activity or may affect activity toward particular cellular substrates. Finally, there is emerging literature to suggest that caspases can participate in a variety of cellular processes unrelated to apoptotic cell death. In these settings, it is particularly important that caspases are maintained under stringent control to avoid inadvertent cell death. It is likely that continued examination of these processes will reveal new mechanisms of caspase regulation with implications well beyond control of apoptotic cell death.

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“…Binding of the receptor induces a clustering (typically a trimerization), and subsequent formation of a death inducing signal complex, dependent on uniting the intracellular death domains of each receptor subunit (Curtin et al, 2003). Via the adaptor molecule Fas-associated death domain protein (FADD), the death complex recruits multiple procaspase-8 molecules, bringing them close enough together to induce auto-cleavage by proximity .…”

Section: Apoptosis: Generalmentioning

confidence: 99%