IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond

Joseph, Suresh K.; Hajnóczky, György

doi:10.1007/s10495-007-0719-7

Cited by 149 publications

(126 citation statements)

References 171 publications

(219 reference statements)

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“…This idea is supported by observations that modulation of IP 3 R activity (by antisense knockdown, genetic deletion, or using a cell-permeable inhibitory peptide that interferes with the IP 3 R-cytochrome c interaction) rendered cells less sensitive to apoptosis triggered by both intrinsic and extrinsic pathways (Joseph and Hajnoczky, 2007). Moreover, Bcl-2 and Bcl-X L , two major antiapoptotic proteins, interact with the IP 3 R and alter its activity, though in opposite ways: Bcl-2 decreases the IP 3 R opening probability, whereas Bcl-X L increases it (Oakes et al, 2003;Chen et al, 2004;White et al, 2005).…”

Section: Discussionmentioning

confidence: 86%

Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes

Mattia¹,

Gubser

Dommelen³

et al. 2009

MBoC

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Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that is highly conserved in eukaryotes and present in some poxviruses, but its molecular mechanism is unknown. Given that alterations in intracellular Ca 2؉ homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca 2؉ signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca 2؉ influx from the extracellular space. In addition, it reduced histamine-induced Ca 2؉ release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca 2؉ fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca 2؉ . Overexpression of h-GAAP lowered the Ca 2؉ content of the intracellular stores and decreased the efficacy of IP 3 , providing possible explanations for the observed results. Opposite effects were obtained when h-GAAP was knocked down by siRNA. Thus, our data demonstrate that h-GAAP modulates intracellular Ca 2؉ fluxes induced by both physiological and apoptotic stimuli.

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Section: Discussionmentioning

confidence: 86%

Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes

Mattia¹,

Gubser

Dommelen³

et al. 2009

MBoC

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“…Moreover, numerous reports have suggested that altered IP 3 R activity is involved in apoptosis in a variety of cell types (reviewed in Ref. 16). For example, initial reports showed that IP 3 Rs are required to promote apoptosis.…”

mentioning

confidence: 99%

“…Despite these reports questions remain. For example, what is the fate of the expected N-terminal fragment (16)? It is also not clear whether all of the subunits within individual tetrameric channels are cleaved during caspase proteolysis of IP 3 R1.…”

mentioning

confidence: 99%

Fragmented Inositol 1,4,5-Trisphosphate Receptors Retain Tetrameric Architecture and Form Functional Ca2+ Release Channels

Alzayady

Chandrasekhar

Yule

2013

Journal of Biological Chemistry

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Background: Proteolytic cleavage and disruption of inositol 1,4,5-trisphosphate receptor (IP 3 R) architecture may contribute to the initiation/progression of apoptosis. Results: Proteolytic cleavage products of the IP 3 R remain membrane-associated, and these fragments form functional tetrameric channels. Conclusion: Fragmentation of the IP 3 R does not inevitably lead to loss of function. Significance: Peptide continuity is not required for IP 3 R function, and IP 3 R activation may persist after protease cleavage during apoptosis.

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“…IP3Rs are ligand-gated channels that serve to discharge Ca 2 þ from ER stores in response to agonist stimulation. 40,54 After IP3-mediated release of Ca 2 þ from the ER through the IP3 receptor, high-Ca 2 þ microdomains (estimated to be in the range of 50-100 mM) are generated at the tight ERmitochondrial junctions, activating the low-affinity mitochondrial Ca 2 þ uniporter and resulting in mitochondrial Ca 2 þ uptake 32 ( Figure 4).…”

Section: Ip3rs As Target Of Cell Deathmentioning

confidence: 99%

The role of PML in the control of apoptotic cell fate: a new key player at ER–mitochondria sites

2011

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The development of malignant tumors results from deregulated proliferation or an inability of cells to undergo apoptotic cell death. Experimental works of the past decade have highlighted the importance of calcium (Ca 2 þ ) in the regulation of apoptosis. Several studies indicate that the Ca 2 þ content of the endoplasmic reticulum (ER) determines the cell's sensitivity to apoptotic stress and perturbation of ER Ca 2 þ homeostasis appears to be a key component in the development of several pathological situations. Sensitivity to apoptosis depends on the ability of cells to transfer Ca 2 þ from the ER to the mitochondria. The physical platform for the interplay between the ER and mitochondria is a domain of the ER called the mitochondria-associated membranes (MAMs). The disruption of these contact sites has profound consequences for cellular function, such as imbalances of intracellular Ca 2 þ signaling, cellular stress, and disrupted apoptosis progression. The promyelocytic leukemia (PML) protein has been previously recognized as a critical and essential regulator of multiple apoptotic response. Nevertheless, how PML would exert such broad and fundamental role in apoptosis remained for long time a mystery. In this review, we will discuss how recent results demonstrate that the elusive mechanism whereby the PML tumor suppressor exerts its essential role in apoptosis triggered by Ca 2 þ -dependent stimuli can be attributed to its unexpected and fundamental role at MAMs in the control of the functional cross-talk between ER and mitochondria. The Promyelocytic Leukemia ProteinThe promyelocytic leukemia (PML) protein is a tumor suppressor gene originally identified at the break point of the t(15;17) chromosomal translocation of acute promyelocytic leukemia (APL), a distinct subtype of acute myeloid leukemia. As a consequence of this translocation, PML fuses to the retinoic acid (RA) receptor alpha (RARa) gene. Two fusion genes are generated encoding PML-RARa and RARa-PML fusion proteins, which coexist in the leukemic cells, blocking heamatopoietic differentiation (for a review, see Pandolfi; 1 Salomoni and Pandolfi. 2 PML has, therefore, become the object of intense research on the basis of this premise. Since then, PML has been shown to regulate diverse cellular functions, such as transcriptional regulation, DNA-damage response, sumoylation process, cellular senescence, neoangiogenesis, and, of relevance to this review, apoptosis. 3,4 PML belongs to a large family of proteins harboring a tripartite structure that contains a zinc-finger called the RING motif (R) located N-terminally followed by two additional zincfingers motifs (B-boxes; B) and an a-helical coiled-coil domain (CC), collectively referred to as the RBCC domain. The RBCC domain mediates protein-protein interactions and is responsible for PML multimerization and the formation of macromolecular complexes. The C-terminal region of PML is less structured and varies between PML isoforms. Alternative splicing of C-terminal exons is responsible for the existen...

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IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond

Cited by 149 publications

References 171 publications

Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes

Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes

Fragmented Inositol 1,4,5-Trisphosphate Receptors Retain Tetrameric Architecture and Form Functional Ca2+ Release Channels

The role of PML in the control of apoptotic cell fate: a new key player at ER–mitochondria sites

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