The nucleolus: A new home for the PIDDosome

Bouchier‐Hayes, Lisa; Sidi, Samuel

doi:10.1080/15384101.2017.1355179

Cited by 2 publications

(3 citation statements)

References 7 publications

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“…At the same time, although some reports suggested nuclear localization of caspase-8 and -9 13 , 14 , 25 , caspase-2 is the only initiator caspase for which nuclear localization has been described as a way of regulating its functions 26 , 27 . However, the data on caspase-2 cellular distribution and its activation site remain controversial 28 – 32 , although the recent findings have significantly improved our current understanding 27 , 33 . In most of the previous studies on caspase-2 localization, the authors used ectopical expression of caspase-2 linked to a fluorescent protein, e.g.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis regulation by subcellular relocation of caspases

Prokhorova

Kopeina

Lavrik

et al. 2018

Sci Rep

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The cleavage of nuclear proteins by caspases promotes nuclear breakdown and, therefore, plays a key role in apoptosis execution. However, the detailed molecular mechanisms of these events remain unclear. To get more insights into the mechanisms of nuclear events during apoptosis we set up a rapid fractionation protocol for the separation of the cytoplasmic and nuclear fractions of cells undergoing cisplatin-induced apoptosis. Importantly, nuclear accumulation of effector caspase-3 as well as initiator caspase-2, -8 and -9 was observed using the developed protocol and immunofluorescence microscopy. The detection of caspases and their cleavage products in the nucleus occurred within the same time interval after cisplatin treatment and took place shortly before nuclear fragmentation. The entry of initiator caspases to the nucleus was independent of caspase-3. Given that all three initiator caspases had catalytic activity in the nuclei, our findings indicate that initiator caspases might participate in the proteolysis of nuclear components during apoptosis, promoting its disintegration and apoptotic cell death.

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Section: Introductionmentioning

confidence: 99%

Apoptosis regulation by subcellular relocation of caspases

Prokhorova

Kopeina

Lavrik

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Caspase 2, deemed to be a minor caspase in mammalian cells, is activated on a high molecular weight platform known as the PIDDosome (30,31,35), which is assembled when PIDD binds RAIDD (29). Both cytoplasmic and nucleolar compartments act as "homes" for the assembly of PIDDosome complexes (18,(47)(48)(49). In the current study, we focus on PIDDosome assembly in the nucleoplasm/chromatin during the time-course of ATR kinase inhibition achieved using a specific pharmacological inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…Western blotting and IF assays revealed that PIDDosome signalling was indeed activated leading to the cleavage of caspase 2 during ATR and Chk1 kinase inhibition (Fig 3a-e) even under the conditions in which the p53 protein level had fallen to basal values (Fig 1c, 2a). Current models suggest that the PIDDosome complex is activated leading to caspase 2 cleavage in the nucleolar compartment during DNA damage and a similar PIDDosome response recurs in the cytoplasmic compartment during the conditions of cytoskeletal poisoning/disruption (18,46,48,49). In addition, IF analyses of nucleolar markers such as nucleolin, fibrillarin and nucleophosmin revealed that nucleolar structure was distorted during the prolonged inhibition of ATR kinase activity in the cells (Additional file 2a, Fig 3c, 4c) whose effect was specific to ATR and Chk1 rather than DDR apical kinases (ATM and DNAPKc) inhibition (Additional file 2a).…”

Section: Chk1 Undergoes Atr Dependent Phosphorylation At S345 (3)mentioning

confidence: 99%