Prion Protein Prevents Human Breast Carcinoma Cell Line from Tumor Necrosis Factor α-Induced Cell Death

Diarra‐Mehrpour, Maryam; Arrabal, Samuel; Jalil, Abdelali; Pinson, Xavier; Gaudin, Catherine; Piétu, Geneviève; Pitaval, Amandine; Ripoche, Hugues; Éloit, Marc; Dormont, Dominique; Chouaı̈b, Salem

doi:10.1158/0008-5472.can-03-1735

Cited by 113 publications

(104 citation statements)

References 33 publications

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“…To determine if the antiBax function of PrP is specific to human neurons, we studied MCF-7 cells, where PrP was found to protect against TNFainduced cell death. 7 PrP maintains its protection against Baxmediated cell death in the MCF-7 cells as does Bcl-2, allowing us to use these as a model cell line to study the effects of PrP (Figure 1b). We then investigated if PrP could prevent cell death mediated by tBid, a BH3-only proapoptotic Bcl-2 protein that activates both Bax and Bak.…”

Section: Prp Prevents Bax But Not Bak-or Tbid-mediated Cell Death In mentioning

confidence: 99%

“…1,2 PrP prevents anisomycin-mediated cell death in the neuroblastic layer of mouse retinal explants, 3,4 Doppel-and N-terminally truncated PrP-induced neurodegeneration in mice, 5,6 and tumor necrosis factor a (TNFa)-induced apoptosis in MCF-7 cells. 7 We have shown that both wild-type and cytosolic PrP completely inhibit Bcl-2-associated protein X (Bax)-mediated cell death in human neurons in primary cultures. 8,9 However, whether PrP inhibits upstream or downstream of Bax activation is not known.…”

Section: Introductionmentioning

confidence: 99%

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Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells

et al. 2005

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Prion protein (PrP) prevents Bcl-2-associated protein X (Bax)-mediated cell death, but the step at which PrP inhibits is not known. We first show that PrP is very specific for Bax and cannot prevent Bak (Bcl-2 antagonist killer 1)-, tBid-, staurosporine-or thapsigargin-mediated cell death. As Bax activation involves Bax conformational change, mitochondrial translocation, cytochrome c release and caspase activation, we investigated which of these events was inhibited by PrP. PrP inhibits Bax conformational change, cytochrome c release and cell death in human primary neurons and MCF-7 cells. Serum deprivation-induced Bax conformational change is more rapid in PrP-null cells. PrP does not prevent active caspase-mediated cell death. PrP does not colocalize with Bax in normal or apoptotic primary neurons and cannot prevent Bax-mediated cytochrome c release in a mitochondrial cell-free system. We conclude that PrP protects against Bax-mediated cell death by preventing the Bax proapoptotic conformational change that occurs initially in Bax activation.

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Section: Prp Prevents Bax But Not Bak-or Tbid-mediated Cell Death In mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells

et al. 2005

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“…PrP also binds Grb2, an adapter protein, lipids, and nucleic acids (15)(16)(17). PrP plays a role in apoptosis in a cell context-dependent manner (18)(19)(20)(21)(22). PrP is involved in the proliferation of epithelial cells and in the distribution of junction associated proteins in human enterocytes in vitro and in intestine in vivo (23).…”

Section: Introductionmentioning

confidence: 99%

Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer

Li¹,

Yu²,

Nakamura³

et al. 2009

J. Clin. Invest.

127

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The cellular prion protein (PrP) is a highly conserved, widely expressed, glycosylphosphatidylinositolanchored (GPI-anchored) cell surface glycoprotein. Since its discovery, most studies on PrP have focused on its role in neurodegenerative prion diseases, whereas its function outside the nervous system remains unclear. Here, we report that human pancreatic ductal adenocarcinoma (PDAC) cell lines expressed PrP. However, the PrP was neither glycosylated nor GPI-anchored, existing as pro-PrP and retaining its GPI anchor peptide signal sequence (GPI-PSS). We also showed that the PrP GPI-PSS has a filamin A-binding (

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“…8). It has been reported that PrP c protects against tumor necrosis factor ␣- (9) and Bax-induced cell death (10,11), although this phenotype varies according to the cell type (12). Conversely, we recently established that PrP c overexpression led to an increased staurosporine-evoked cell death (13) in transfected or inducible cell lines and showed that this cellular response was associated with an activation of caspase-3 linked to a transcriptional and post-transcriptional control of the p53 transcription factor (14).…”

mentioning

confidence: 99%

The C-terminal Products of Cellular Prion Protein Processing, C1 and C2, Exert Distinct Influence on p53-dependent Staurosporine-induced Caspase-3 Activation

Sunyach¹,

Cissé

Costa

et al. 2007

Journal of Biological Chemistry

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The cellular prion protein (PrP c ) undergoes various endoproteolytic attacks within its N-terminal domain, leading to the production of C-terminal fragments (C) tethered to the plasma membrane and soluble N-terminal peptides (N). One of these cleavages occurs at position 110/111, thereby generating C1 and N1 products. We have reported that disintegrins ADAM-10, -9, and -17 participate either directly or indirectly to this proteolytic event. An alternative proteolytic event taking place around residue 90 yields C2 and N2 fragments. The putative function of these proteolytic fragments remained to be established. We have set up two novel human embryonic kidney 293 cell lines stably overexpressing either C1 or C2. We show that C1 potentiates staurosporine-induced caspase-3 activation through a p53-dependent mechanism. Thus, C1 positively controls p53 transcription and mRNA levels and increases p53-like immunoreactivity and activity. C1-induced caspase-3 activation remained unaffected by the blockade of endocytosis in HEK 293 cells and was abolished in p53-deficient fibroblasts. Conversely, overexpression of the C2 fragment did not significantly sensitize HEK 293 cells to apoptotic stimuli and did not modify p53 mRNA levels or activity. Therefore, the nature of the proteolytic cleavage taking place on PrP c yielded C-terminal catabolites with distinct function and could be seen as a switch mechanism controlling the function of the PrP c in cell survival.

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Prion Protein Prevents Human Breast Carcinoma Cell Line from Tumor Necrosis Factor α-Induced Cell Death

Cited by 113 publications

References 33 publications

Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells

Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells

Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer

The C-terminal Products of Cellular Prion Protein Processing, C1 and C2, Exert Distinct Influence on p53-dependent Staurosporine-induced Caspase-3 Activation

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