Bcl-2–regulated apoptosis and cytochrome <i>c</i> release can occur independently of both caspase-2 and caspase-9

Marsden, Vanessa S.; Ekert, Paul G.; Delft, Mark F. van; Vaux, David L.; Adams, Jerry M.; Strasser, Andreas

doi:10.1083/jcb.200312030

Cited by 94 publications

(72 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other Bcl-2 sensitive cell death pathways that are independent of Apaf-1 have been identified in other systems further supporting this idea. 38,39 Though APAF-1 deficient cells displayed reduced sensitivity to nuclear TRADD-induced death, the finding that zVAD.fmk but not AEBSF cooperates with APAF-deficiency to confer complete resistance suggests that the AEBSF-sensitive pathway is APAF-1 dependent.…”

Section: Discussionmentioning

confidence: 99%

The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

TNFR1 associated death domain protein (TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain along with nuclear import and export sequences that cause shuttling between the cytoplasm and nucleus. The death domain of TRADD contains the nuclear import sequence and expression of the core death domain (nuclear TRADD) results in exclusive nuclear localization and activation of a distinct apoptotic pathway. Cytoplasmic TRADD activates apoptosis through Fas-associated death domain protein (FADD) and caspase-8 activation that was blocked by caspase inhibitors or dominant-negative FADD. These inhibitors did not inhibit death induced by nuclear TRADD, which could only be inhibited by combining caspase inhibitors and a serine protease inhibitor. The pathway activated by nuclear TRADD requires caspase-9 catalytic activity. However, apoptosis activating factor deficiency confers only partial protection from death. This pathway represents an alternate means by which TRADD can regulate cell death independently of FADD and caspase-8 that occurs from the nucleus rather than the cytoplasm.

show abstract

Section: Discussionmentioning

confidence: 99%

The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…75 The Apaf-1/caspase-9 pathway also appears to be dispensable for the apoptosis of many haematopoietic lineages and loss of either caspase-9 or Apaf-1 only delays apoptosis but fails to provide clonogenic survival of cells. [76][77][78][79] These data suggest that caspase-9/Apaf-1 pathway is not essential for normal animal development or cell death and the genetic background of mice is a major factor in many of the observed phenotypes.…”

Section: The Mammalian Apoptotic Caspasesmentioning

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

“…16 Further, Casp2 À / À ; Casp9 À / À double knockout mice are indistinguishable from Casp9 À / À mice in terms of their development and show embryonic brain malformation and perinatal lethality. 17 In addition, Casp2 À / À ; Casp9 À / À hematopoietic cells develop normally, and lymphocytes and fibroblasts lacking both caspases remain sensitive to many apoptotic stimuli, showing release of cytochrome c from mitochondria. 17 On the other hand, Casp2 À / À mouse embryonic fibroblasts (MEFs) show subtle resistance to killing by heat-shock and cytoskeletal-disrupting chemotherapeutic agents.…”

Section: Caspase-2 Knockout Micementioning

confidence: 99%

“…17 In addition, Casp2 À / À ; Casp9 À / À hematopoietic cells develop normally, and lymphocytes and fibroblasts lacking both caspases remain sensitive to many apoptotic stimuli, showing release of cytochrome c from mitochondria. 17 On the other hand, Casp2 À / À mouse embryonic fibroblasts (MEFs) show subtle resistance to killing by heat-shock and cytoskeletal-disrupting chemotherapeutic agents. 18,19 Interestingly, in Casp2 À / À neurons, NGF-deprivation-induced cell death is dependent on the caspase-9 pathway.…”

Section: Caspase-2 Knockout Micementioning

confidence: 99%

Caspase-2 as a tumour suppressor

2013

View full text Add to dashboard Cite

Ever since its discovery 20 years ago, caspase-2 has been enigmatic and its function somewhat controversial. Although many in vitro studies suggested that caspase-2 was important for apoptosis, demonstrating an in vivo cell death role for this caspase has been more problematic, with caspase-2-deficient mice showing limited, tissue-specific cell death defects. Recent results from different laboratories suggest that at least one of its physiological roles in animals is to protect against cellular stress and transformation. As such, loss of caspase-2 augments tumorigenesis in some mouse models of cancer, assigning a tumour suppressor function to this enigmatic caspase. This review focuses on this seemingly non-apoptotic function of caspase-2 as a tumour suppressor and reconciles some of the recent findings in the field.

show abstract

Bcl-2–regulated apoptosis and cytochrome c release can occur independently of both caspase-2 and caspase-9

Cited by 94 publications

References 34 publications

The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm

The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm

Caspase function in programmed cell death

Caspase-2 as a tumour suppressor

Contact Info

Product

Resources

About