Caspase-3/CPP32-like activity is not sufficient to mediate apoptosis in an IL-2 dependent T cell line

Vasilakos, John P.; Lynch, Timothy P.; Ghayur, Tariq; Giegel, David A.; Santoro, Maxine Fico; Shivers, Brenda D.

doi:10.1023/a:1026489104188

Cited by 5 publications

(6 citation statements)

References 64 publications

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“…In these studies, apoptosis was monitored by metabolism of the dye AlamarBlue (41). Recently, Vasilakos et al (42), demonstrated that cell death data obtained with AlamarBlue correlated well with data obtained in the same experiment by monitoring trypan blue exclusion as an index of cell viability. In addition, positive correlation between AlamarBlue and several other parameters of apoptosis, such as caspase-3 activation, DNA laddering, and nuclear condensation, were demonstrated.…”

Section: Pp2a Competes As a Substrate In Two Caspase-3 Assay Systems-mentioning

confidence: 54%

Regulation of Protein Phosphatase 2A Activity by Caspase-3 during Apoptosis

Santoro¹,

Annand²,

Robertson³

et al. 1998

Journal of Biological Chemistry

150

100

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Although the available evidence suggests that whereas the caspase family plays a major role in apoptosis, they are not the sole stimulators of death. A random yeast two-hybrid screen of a lymphocyte cDNA library (using caspase-3 as the bait) found an interaction between caspase-3 and the regulatory subunit A␣ of protein phosphatase 2A. This protein was found to be a substrate for caspase-3, but not caspase-1, and could compete effectively against either a protein or synthetic peptide substrate.In Jurkat cells induced to undergo apoptosis with anti-Fas antibody, protein phosphatase 2A (PP2A) activity increased 4.5-fold after 6 h. By 12 h, the regulatory A␣ subunit could no longer be detected in cell lysates. There was no change in the amount of the catalytic subunit. The effects on PP2A could be prevented by the caspase family inhibitors acetyl-Asp-Glu-Val-Asp (DEVD) aldehyde or Ac-DEVD fluoromethyl ketone. The mitogen-activated protein (MAP) kinase pathway is regulated by PP2A. At 12 h after the addition of anti-Fas antibody, a decrease in the amount of the phosphorylated forms of MAP kinase was observed. Again, this loss of activated MAP kinase could be prevented by the addition of DEVD-cho or DEVD-fmk. These data are consistent with a pathway whereby induction of apoptosis activates caspase-3. This enzyme then cleaves the regulatory A␣ subunit of PP2A, increasing its activity. These data show that the activated PP2A will then effect a change in the phosphorylation state of the cell. These data provide a link between the caspases and signal transduction pathways.

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Section: Pp2a Competes As a Substrate In Two Caspase-3 Assay Systems-mentioning

confidence: 54%

Regulation of Protein Phosphatase 2A Activity by Caspase-3 during Apoptosis

Santoro¹,

Annand²,

Robertson³

et al. 1998

Journal of Biological Chemistry

150

100

View full text Add to dashboard Cite

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“…Caspases 3 and 7 had very potent IRS-1-degrading activity, and caspase 10 had significant but weaker IRS-1-degrading activity. To determine whether caspases 3 and 7 mediated hypoxia-induced cleavage of IRS-1 in cells, we incubated hypoxic cells with Z-DEVD-fmk, an inhibitor of caspases 3 and 7 (50). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Oxygen Tension Regulates the Stability of Insulin Receptor Substrate-1 (IRS-1) through Caspase-mediated Cleavage

Kang

Brown

Chung

2007

Journal of Biological Chemistry

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The insulin and insulin-like growth factor-1 (IGF-1) receptors mediate signaling for energy uptake and growth through insulin receptor substrates (IRSs), which interact with these receptors as well as with downstream effectors. Oxygen is essential not only for ATP production through oxidative phosphorylation but also for many cellular processes, particularly those involved in energy homeostasis. The oxygen tension in vivo is significantly lower than that in the air and can vary widely depending on the tissue as well as on perfusion and oxygen consumption. How oxygen tension affects IRSs and their functions is poorly understood. Our findings indicate that transient hypoxia (1% oxygen) leads to caspase-mediated cleavage of IRS-1 without inducing cell death. The IRS-1 protein level rebounds rapidly upon return to normoxia. Protein tyrosine phosphatases (PTPs) appear to be important for the IRS-1 cleavage because tyrosine phosphorylation of the insulin receptor was decreased in hypoxia and IRS-1 cleavage could be blocked either with H 2 O 2 or with vanadate, each of which inhibits PTPs. Activity of Akt, a downstream effector of insulin and IGF-1 signaling that is known to suppress caspase activation, was suppressed in hypoxia. Overexpression of dominant-negative Akt led to IRS-1 cleavage even in normoxia, and overexpression of constitutively active Akt partially suppressed IRS-1 cleavage in hypoxia, suggesting that hypoxiamediated suppression of Akt may induce caspase-mediated IRS-1 cleavage. In conclusion, our study elucidates a mechanism by which insulin and IGF-1 signaling can be matched to the oxygen level that is available to support growth and energy metabolism.

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“…41 ± 44 This suggests that this pathway is still activated in the cell but it is not the pathway that actually kills the cell, perhaps because it is not sufficient to mediate apoptosis in this metabolic state, as it has already been suggested in other cell lines. 45 Alternatively, caspase 3 may be activated by a caspase 1-independent pathway, also involved in the activation of LDNase II. This question is under current investigation.…”

Section: Discussionmentioning

confidence: 99%

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

et al. 1999

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We have applied to human HeLa cells two different stimuli of apoptosis: the antitumoral drug etoposide, and a morè physiological' death condition, obtained by growing cells in the same medium for long time periods, for up to 10 days. Analysis of different parameters demonstrated that in both experimental systems the same apoptotic features are visible. However, the DNA degradation pattern appeared to be different, suggesting the involvement of different DNases. In this view, we have analyzed the activity and expression of Ca 2+ -Mg 2+ -dependent and acid DNases. We have observed that DNase I is not modulated during apoptosis. In contrast, the acid L-DNase II (derived from Leukocyte Elastase Inhibitor by post-translational modification), recently identified in our laboratory, is mainly active in the apoptotic pathway induced by long term-culture. Furthermore, we have provided evidence that while caspase 3 is activated by both inducers, caspase 1 is essential only for the etoposide-induced apoptosis.

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Caspase-3/CPP32-like activity is not sufficient to mediate apoptosis in an IL-2 dependent T cell line

Cited by 5 publications

References 64 publications

Regulation of Protein Phosphatase 2A Activity by Caspase-3 during Apoptosis

Regulation of Protein Phosphatase 2A Activity by Caspase-3 during Apoptosis

Oxygen Tension Regulates the Stability of Insulin Receptor Substrate-1 (IRS-1) through Caspase-mediated Cleavage

Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture

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