Cited by 1,267Cell death mechanisms and regulationInflammasome and immune disordersCalpain Protease Function and Regulation

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Old, new and emerging functions of caspases

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Shalini, S, Dorstyn, L, Dawar, S, Kumar, S·2015·Cell Death & Differentiation

DOI 10.1038/cdd.2014.216PMC PMC4356345

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Abstract

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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Authors: Shalini, S., Dorstyn, L., Dawar, S., & Kumar, S.
Affiliations: University of South Australia (AU)
Corresponding author: Kumar, S
ORCID: Dorstyn, L
Dawar, S
Kumar, S
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2014-12-19
Volume: 22
Issue: 4
Pages: 526-539
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/cdd.2014.216
PMC: PMC4356345
OpenAlex: W2016540525
Cited by: 1,267
References: 205
Citations by year: 2026: 45 · 2025: 80 · 2024: 140 · 2023: 116 · 2022: 142 · 2021: 152 · 2020: 154 · 2019: 130 · 2018: 79 · 2017: 87 · 2016: 89 · 2015: 50 · 2014: 1
FWCI: 7.12
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Cell Death and Differentiation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders: Medical Research Council
National Health and Medical Research Council (1041807, 1002863, 1043057, 1021456)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
Keywords: caspases, non-apoptotic caspase function, caspase-1, caspase-11, pyroptosis, caspase-8, necroptosis, caspase-3, caspase-2, CASP14, inflammation, tumor suppression, tumor progression, genome stability, autophagy, aging, tissue regeneration, neural development
MeSH terms: Animals, Cell Differentiation, Humans, Regeneration, Apoptosis, Inflammation Mediators, Caspases, Genomic Instability, Carcinogenesis

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