Caspase Functions in Cell Death and Disease

McIlwain, David R.; Berger, Thorsten; Mak, Tak W.

doi:10.1101/cshperspect.a008656

Cited by 1,872 publications

(1,488 citation statements)

References 262 publications

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“…8 It is also important to note that caspase-5 is not present in mice and caspase-11 and -13 are the murine and bovine orthologues of caspase-4, respectively. 8,9 Caspase-12 exists in both truncated and full-length alleles in humans and as a full-length caspase in rodents. 10 Caspase-14 is expressed in the epidermis and has a primary role in cornification and protection of underlying layers of skin.…”

Section: Open Questionsmentioning

confidence: 99%

“…76 Mutations in caspase-8 (and caspase-10) are also associated with autoimmune lymphoproliferative syndrome (ALPS). 9 Detailed understanding of the regulation of caspase activation during inflammation and secretion of pro-inflammatory cytokines will potentially provide new avenues for treatment of inflammatory and infectious diseases.…”

Section: Caspases In Inflammation and Immunitymentioning

confidence: 99%

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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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Section: Open Questionsmentioning

confidence: 99%

Section: Caspases In Inflammation and Immunitymentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

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“…Caspases are cysteinyl aspartate-specific proteases that play a pivotal role in the induction of apoptotic cell death (McIlwain et al 2013). The first caspase identified in mammalian cells was the interleukin (IL)-1b-converting enzyme (ICE, now known as caspase-1).…”

Section: Introductionmentioning

confidence: 99%

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Uchiyama

Tsutsui

2014

Arch. Immunol. Ther. Exp.

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“…Caspases, a family of cysteine proteases, are central regulators of apoptosis (14). Caspases hydrolyze peptide bonds after certain aspartic acid residues in the substrate.…”

Section: Introductionmentioning

confidence: 99%

Heat shock protein 20 (HSPB6) regulates apoptosis in human hepatocellular carcinoma cells: Direct association with Bax

et al. 2014

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Abstract.A small heat shock protein (HSP), HSP20 (HSPB6) is ubiquitously expressed in various tissues and has several functions. We previously reported that the expression of HSP20 protein in human hepatocellular carcinoma (HCC) cells is inversely proportional to the progression of HCC. In addition, we showed that HSP20 is associated with phosphoinositide 3-kinase (PI3K) and inhibits the proliferation of HCC cells via suppression of the AKT signaling pathway. However, the relationship between HSP20 and apoptosis in HCC has not yet been elucidated. To clarify whether HSP20 is implicated in the apoptosis of HCC cells, in the present study, we examined the effect of HSP20 on caspases, the central regulators of apoptosis, using human HCC-derived HuH7 cells that are transfected with wild-type human HSP20 (HSP20-overexpressing cells). The cleavage of caspase-3 and caspase-7 in HSP20-overexpressing cells was enhanced compared with the empty vector-transfected cells (control cells). In addition, the cleavage of nuclear poly (ADP-ribose) polymerase (PARP) in HSP20-overexpressing cells was also strengthened. We further investigated the direct targets of HSP20 focusing on Bcl-2 family proteins in the HSP20-overexpressing cells. HSP20 proteins in the cells were coimmunoprecipitated with Bax. On the contrary, Bad, Bcl-2 and Bcl-xL were not coimmunoprecipitated with HSP20. These findings strongly suggest that HSP20 directly associates with Bax and stimulates caspase cascade in human HCC cells.

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Caspase Functions in Cell Death and Disease

Cited by 1,872 publications

References 262 publications

Old, new and emerging functions of caspases

Old, new and emerging functions of caspases

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Heat shock protein 20 (HSPB6) regulates apoptosis in human hepatocellular carcinoma cells: Direct association with Bax

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