A Role for Caspases in Lens Fiber Differentiation

Ishizaki, Yasuki; Jacobson, Marcus; Raff, Martin

doi:10.1083/jcb.140.1.153

Cited by 258 publications

(197 citation statements)

References 43 publications

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“…23 Caspases have also been shown to be activated as part of the denucleation process during the terminal differentiation of lens epithelial cells. 24 Similarly, active caspases are detected following T-lymphocyte stimulation in the absence of apoptosis, suggesting a regulatory role during this process. 25,26 Once activated, caspases that have fulfilled their regulatory functions would need to be eliminated to avoid driving the cells into apoptosis.…”

Section: Discussionmentioning

confidence: 98%

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors

et al. 2004

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The activation of caspase-3 represents a critical step in the pathways leading to the biochemical and morphological changes that underlie apoptosis. Upon induction of apoptosis, the large (p17) and small (p12) subunits, comprising active caspase-3, are generated via proteolytic processing of a latent proenzyme dimer. Two copies of each individual subunit are generated to form an active heterotetramer. The tetrameric form of caspase-3 cleaves specific protein substrates within the cell, thereby producing the apoptotic phenotype. In contrast to the proenzyme, once activated in HeLa cells, caspase-3 is difficult to detect due to its rapid degradation. Interestingly, however, enzyme stability and therefore detection of active caspase-3 by immunoblot analysis can be restored by treatment of cells with a peptide-based caspase-3 selective inhibitor, suggesting that the active form can be stabilized through protein-inhibitor interaction. The heteromeric active enzyme complex is necessary for its stabilization by inhibitors, as expression of the large subunit alone is not stabilized by the presence of inhibitors. Our results show for the first time, that synthetic caspase inhibitors not only block caspase activity, but may also increase the stability of otherwise rapidly degraded mature caspase complexes. Consistent with these findings, experiments with a catalytically inactive mutant of caspase-3 show that rapid turnover is dependent on the activity of the mature enzyme. Furthermore, turnover of otherwise stable active site mutants of capase-3 is rescued by the presence of the active enzyme suggesting that turnover can be mediated in trans.

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Section: Discussionmentioning

confidence: 98%

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors

et al. 2004

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“…The DNA fragmentation induced by all the apoptotic stimuli investigated in this report was accompanied by the activation of caspase-3-like protease and cleavage of ICAD. However, caspase activation does not necessarily lead to DNA fragmentation (Ishizaki et al, 1998). Whether any caspaseresistant molecules inhibit CAD's DNase activity, remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Involvement of caspase 3-activated DNase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli

McIlroy

Sakahira

Talanian³

et al. 1999

Oncogene

110

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Degradation of chromosomal DNA into nucleosomesized fragments is one of the characteristics of apoptotic cell death. Here, we examined whether caspase-activated DNase (CAD) is responsible for the DNA fragmentation that occurs upon exposure to various apoptotic stimuli. When human Jurkat cells were exposed to etoposide, or UV or g radiation, a caspase-3-like protease was activated, and nuclear DNA was fragmented. Human TF-1 cells, which are dependent on granulocyte-macrophage colony-stimulating factor (GM ± CSF), also underwent apoptosis accompanied by the activation of caspase-3-like protease and DNA fragmentation, when cultured without the cytokine. Both Jurkat and TF-1 cells expressed two forms of ICAD, ICAD-L and ICAD-S, which were cleaved upon exposure to these apoptotic stimuli. Among eight di erent caspases examined, recombinant caspases 3 and 7 speci®cally cleaved ICAD synthesized in a cell-free system. An expression plasmid containing mouse ICAD-L mutated at the caspase-3-recognition sites was then introduced into Jurkat and TF-1 cells. When the transformants were induced to undergo apoptosis (by treatment with etoposide, UV or g radiation for Jurkat cells, or factor withdrawal for TF-1 cells) they did not show DNA fragmentation, although they still died as a result of these stimuli. These results indicated that CAD, released from ICAD by caspase activation, is involved in the nuclear DNA fragmentation induced by these apoptotic stimuli.

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“…82 A non-apoptotic role for the key effector caspase, caspase-3, was identified in lens fiber formation. 83 The process of differentiation of lens epithelial cell into a lens fiber involves enucleation (loss of nuclei), which was found to be caspase-3 dependent. 83 Other cells that demonstrate enucletion during differentiation include RBCs and keratinocytes.…”

Section: Caspases In Cell-fate Determination and Differentiationmentioning

confidence: 99%

“…83 The process of differentiation of lens epithelial cell into a lens fiber involves enucleation (loss of nuclei), which was found to be caspase-3 dependent. 83 Other cells that demonstrate enucletion during differentiation include RBCs and keratinocytes. Several caspases, including caspase-3, -2, and -9 are transiently activated prior to enucleation during erythroid differentiation and involved cleavage of several proteins such as PARP, acinus and lamin B.…”

Section: Caspases In Cell-fate Determination and Differentiationmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

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Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

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A Role for Caspases in Lens Fiber Differentiation

Cited by 258 publications

References 43 publications

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors

Involvement of caspase 3-activated DNase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli

Old, new and emerging functions of caspases

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