In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis

Tu, S. Sean; McStay, Gavin P.; Boucher, Louis-Martin; Mak, Tak W.; Beere, Helen M.; Green, Douglas R.

doi:10.1038/ncb1340

Cited by 178 publications

(206 citation statements)

References 31 publications

Supporting

Mentioning

199

Contrasting

Order By: Relevance

“…Similarly to our study, a change in the ratio between caspase-8 and c-FLIP within the DISC resulting in enhanced caspase activation and more efficient apoptotic signaling has been shown with 5-fluorouracil treatment (78). It has recently been shown that caspase-2 is activated upon hyperthermia (79) and that caspase-2 is able to prime the cleavage of caspase-8, promoting TRAIL-mediated apoptosis (80). Thereby, caspase-2 could possibly be involved also in the hyperthermia-induced increase in caspase-8 activation and sensitization to CD95-mediated apoptosis.…”

Section: Discussionsupporting

confidence: 86%

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Meinander

Söderström

Kaunisto

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Fever has a major impact on immune responses by modulating survival, proliferation, and endurance of lymphocytes. Lymphocyte persistence in turn is determined by the equilibrium between death and survival-promoting factors that regulate death receptor signaling in these cells. A potential integrator of death receptor signaling is the caspase-8 inhibitor c-FLIP, the expression of which is dynamically regulated, either rapidly induced or down-regulated. In this study, we show in activated primary human T lymphocytes that hyperthermia corresponding to fever triggered down-regulation of both c-FLIP-splicing variants, c-FLIPshort (c-FLIPS) and c-FLIPlong, with consequent sensitization to apoptosis mediated by CD95 (Fas/APO-1). The c-FLIP down-regulation and subsequent sensitization was specific for hyperthermic stress. Additionally, we show that the hyperthermia-mediated down-regulation was due to increased ubiquitination and proteasomal degradation of c-FLIPS, the stability of which we have shown to be regulated by its C-terminal splicing tail. Furthermore, the induced sensitivity to CD95 ligation was independent of heat shock protein 70, as thermotolerant cells, expressing substantially elevated levels of heat shock protein 70, were not rescued from the effect of hyperthermia-mediated c-FLIP down-regulation. Our findings indicate that fever significantly influences the rate of lymphocyte elimination through depletion of c-FLIPS. Such a general regulatory mechanism for lymphocyte removal has broad ramifications for fever-mediated regulation of immune responses.

show abstract

Section: Discussionsupporting

confidence: 86%

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Meinander

Söderström

Kaunisto

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…102,121 Recently Tu et al reported that casp2 À/À MEFs are resistant to apoptosis induced by HS. 109 However, another study by Milleron and Bratton 122 failed to see any role for caspase-2 in HS-induced MEF cell death. The phenotype of casp2/casp9 double KO is similar to casp9 KO, suggesting that these two caspases are unlikely to be functionally redundant.…”

Section: The Apoptotic Caspases S Kumarmentioning

confidence: 99%

“…[102][103][104][105] In some cells, caspase-2 was demonstrated to be required for mitochondrial outer membrane permeabilization (MOMP) and the release of apoptogenic factors in response to DNAdamaging agents. 106 Caspase-2 has also been shown to be necessary for TRAIL-mediated, 107,108 heat shock (HS)-induced apoptosis, 109,110 as well as oocyte cell death. 111 Recently, caspase-2 was shown to associate with Fas/CD95 DISC and get activated in that complex, but apparently not required for CD95-induced cell death.…”

Section: The Apoptotic Caspases S Kumarmentioning

confidence: 99%

Caspase function in programmed cell death

2006

View full text Add to dashboard Cite

The first proapoptotic caspase, CED-3, was cloned from Caenorhabditis elegans in 1993 and shown to be essential for the developmental death of all somatic cells. Following the discovery of CED-3, caspases have been cloned from several vertebrate and invertebrate species. As reviewed in other articles in this issue of Cell Death and Differentiation, many caspases function in nonapoptotic pathways. However, as is clear from the worm studies, the evolutionarily conserved role of caspases is to execute programmed cell death. In this article, I will specifically focus on caspases that function primarily in cell death execution. In particular, the physiological function of caspases in apoptosis is discussed using examples from the worm, fly and mammals.

show abstract

“…Whether or not gluconeogenesisderived glucose-6-phosphate can serve a similar role in tissues such as the liver remains to be examined. Caspase-2 is activated by cellular stress, DNA damage and trophic factor deprivation (Lassus et al, 2002;Tinel and Tschopp, 2004;Zhivotovsky and Orrenius, 2005;Tu et al, 2006) and acts upstream of mitochondria through the activation of 'BH3-only' proteins. It has been shown that caspase-2 can cleave and activate Bid (Guo et al, 2002;Lassus et al, 2002;Robertson et al, 2002;Wagner et al, 2004) and that its proapoptotic activity is dependent on Bid (Gao et al, 2005).…”

Section: Gsh Peroxide Inactivationmentioning

confidence: 99%

Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt

2006

View full text Add to dashboard Cite

Cell survival has been closely linked to both trophic growth factor signaling and cellular metabolism. Such couplings have obvious physiologic and pathophysiologic implications, but their underlying molecular bases remain incompletely defined. As a common mediator of both the metabolic and anti-apoptotic effects of growth factors, the serine/threonine kinase Akt -also known as protein kinase B or PKB -is capable of regulating and coordinating these inter-related processes. The glucose dependence of the antiapoptotic effects of growth factors and Akt plus a strong correlation between Akt-regulated mitochondrial hexokinase association and apoptotic susceptibility suggest a major role for hexokinases in these effects. Mitochondrial hexokinases catalyse the first obligatory step of glucose metabolism and directly couple extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation, and are thus well suited to play this role. The ability of Akt to regulate energy metabolism appears to have evolutionarily preceded the capacity to control cell survival. This suggests that Akt-dependent metabolic regulatory functions may have given rise to glucose-dependent antiapoptotic effects that evolved as an adaptive sensing system involving hexokinases and serve to ensure mitochondrial homeostasis, thereby coupling metabolism to cell survival. We hypothesize that the enlistment of Akt and hexokinase in the control of mammalian cell apoptosis evolved as a response to the recruitment of mitochondria to the apoptotic cascade. The central importance of mitochondrial hexokinases in cell survival also suggests that they may represent viable therapeutic targets in cancer.

show abstract

In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis

Cited by 178 publications

References 31 publications

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Caspase function in programmed cell death

Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt

Contact Info

Product

Resources

About