mRNA expression of caspase 14 in skin epithelial
malignancies

Markiewicz, Agnieszka; Sigorski, Dawid; Markiewicz, Mateusz; Placek, Waldemar; Owczarczyk‐Saczonek, Agnieszka

doi:10.5114/ada.2023.127646

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Caspase-2 will be discussed in detail in the next section (Chapter 1.3). Caspase-12 often gets phylogenetically classified as an inflammatory caspase, although its function remains unclear (Van Opdenbosch & Lamkanfi, 2019), and the deviating caspase-14 has a very particular localisation and is functionally linked to PCD in the process of cornification (Markiewicz et al, 2021).…”

Section: Apoptosismentioning

confidence: 99%

Disruption of p54nrb's gene regulatory function by caspase-2 exhibits a multifaceted role in tumor cell death susceptibility

Eichler¹

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Caspase-2 is the evolutionary most conserved member of the caspase family and was shown to be involved in genotoxic stress induced apoptosis, control of aneuploidy, and ageing related metabolic changes. However, its role in apoptosis seems redundant due to the observation, that knockout does not inhibit apoptotic signalling exclusively. Instead, knockout of caspase-2 leads to tumor susceptibility in vivo, which led to the assumption, that caspase-2 has non-apoptotic functions and can act as a tumor suppressor. The underlying mechanism of the tumor suppressor activity of caspase-2 has not been clarified so far. Furthermore, caspase-2, has a prominent, and as pro-enzyme exclusive localisation in the nucleus and other subcellular compartments, implicating a distinct and location specific role. In this study, a novel caspase-2 specific substrate, termed p54nrb, was identified. P54nrb is harbouring a caspase-2 specific cleavage site at the aspartate residue D422, and cleavage of p54nrb leads apparently to disruption of its putative DNA binding domain at the C-terminus. P54nrb is a nuclear multifunctional RNA and DNA binding protein, known for roles in transcriptional regulation, DNA unwinding and repair, RNA splicing, and retention of defective RNA. Overexpression of p54nrb has been observed in several human cancers, such as cervix carcinoma, melanoma, and colon carcinoma. Data from this study revealed, that depletion of p54nrb in tumor cell lines results in a loss of resistance to drug induced cell death and to reduced capability of anchorage independent growth, which is functionally equivalent to a reduced tumorigenic potential. Meanwhile, p54nrb depletion alone is not cytotoxic. The investigation of p54nrb dependent gene regulations by high resolution quantitative proteomics uncovered an altering expression of multiple tumorigenic genes. For two of these candidates, the tumorigenic protease cathepsin-Z and the anti-apoptotic gelsolin, p54nrb dependent expression was detected universally in all three investigated tumor cell lines, cervix carcinoma, melanoma, and colon carcinoma. Additionally, a direct interaction of p54nrb with the cathepsin Z and gelsolin encoding DNA, but not with their corresponding mRNA, could be demonstrated. Conjointly, this study unveils a novel mechanistic feature of caspase-2 as a tumor suppressor. The caspase-2—p54nrb axis can orchestrate the levels of several tumorigenic proteins and thereby determine the cell death susceptibility and long-term tumor survival. These findings might be of great value for future therapeutic interventions and for overcoming drug resistance of tumors.

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Section: Apoptosismentioning

confidence: 99%

Disruption of p54nrb's gene regulatory function by caspase-2 exhibits a multifaceted role in tumor cell death susceptibility

Eichler¹

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Exploring caspase functions in mouse models

Svandova,

Vesela,

Janeckova

et al. 2024

Apoptosis

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Caspases are enzymes with protease activity. Despite being known for more than three decades, caspase investigation still yields surprising and fascinating information. Initially associated with cell death and inflammation, their functions have gradually been revealed to extend beyond, targeting pathways such as cell proliferation, migration, and differentiation. These processes are also associated with disease mechanisms, positioning caspases as potential targets for numerous pathologies including inflammatory, neurological, metabolic, or oncological conditions. While in vitro studies play a crucial role in elucidating molecular pathways, they lack the context of the body’s complexity. Therefore, laboratory animals are an indispensable part of successfully understanding and applying caspase networks. This paper aims to summarize and discuss recent knowledge, understanding, and challenges in caspase knock-out mice.

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mRNA expression of caspase 14 in skin epithelial malignancies

Cited by 2 publications

References 27 publications

Disruption of p54nrb's gene regulatory function by caspase-2 exhibits a multifaceted role in tumor cell death susceptibility

Disruption of p54nrb's gene regulatory function by caspase-2 exhibits a multifaceted role in tumor cell death susceptibility

Exploring caspase functions in mouse models

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