Signal transduction pathways that regulate cell survival and cell death

Dragovich, Tomislav; Rudin, Charles M.; Thompson, Craig B.

doi:10.1038/sj.onc.1202587

Cited by 170 publications

(100 citation statements)

References 36 publications

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“…Following infection with Ad-mda-7, expression of the tumor suppressor gene p53, whose expression has been shown to induce apoptosis, 12 increased in p53 wt , A549 and H460 tumor cells, but was undetectable in p53 null H1299 cells. Although p53 expression seemed slightly up-regulated in Ad-Luc-infected p53 wt cells (A549 and H460) as compared with PBS control, a 5.4-fold increase in p53 expression was observed in Ad-mda-7-infected tumor cells when compared with Ad-Luc-infected cells.…”

Section: Figure 6 Inhibition Of Apoptosis By Pancaspase Inhibitor Z-vmentioning

confidence: 99%

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

et al. 2000

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The melanoma differentiation-associated gene-7 (mda-7), cloned from a human melanoma cell line H0-1, is known to induce tumor cell-selective growth inhibition in breast cancer cells in vitro and loss of tumorigenicity ex vivo. Yet, the mechanisms underlying these effects are still unknown. Therefore, we investigated these mechanisms on the molecular level in human non-small cell lung carcinoma (NSCLC) cells in vitro. Overexpression of mda-7 protein by Ad-mda-7 significantly suppressed proliferation and induced G2/M cell cycle arrest in wild-type p53 (A549, H460), and p53-null (H1299) non-small cell lung cancer cell lines, but not in normal human lung fibroblast (NHLF) cells. p53, Bax,

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Section: Figure 6 Inhibition Of Apoptosis By Pancaspase Inhibitor Z-vmentioning

confidence: 99%

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

et al. 2000

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“…Apoptosome-mediated caspase-9 cleavage then leads to the activation of effector caspases (caspase-3, caspase-6 and caspase-7), resulting in cell death. 1,4,8 The second apoptotic pathway involves signaling by cell surface death receptors such as TNFR-1 or Fas, which, through adaptor molecules, promote caspase-8 cleavage, leading to apoptosis. 1,8 In both pathways, activated caspase-3, one of the final products of the protease cascade, can cleave a number of key cellular proteins including poly(ADP-ribose) polymerase, an enzyme important for DNA repair.…”

Section: Introductionmentioning

confidence: 99%

Effect of staurosporine-induced apoptosis on endothelial nitric oxide synthase in transfected COS-7 cells and primary endothelial cells

2005

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Nitric oxide (NO) may block apoptosis by inhibiting caspases via S-nitrosylation of cysteines. Here, we investigated whether effector caspases might cleave and thereby inhibit endothelial nitric oxide synthase (eNOS). Exposure of eNOS-transfected COS-7 cells and bovine aortic endothelial cells to staurosporine resulted in significant loss of 135-kDa eNOS protein and activity, and appearance of a 60-kDa eNOS fragment; effects were inhibited by the general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp[OMe]-fluoromethyl ketone (zVAD-fmk). In eNOS-transfected COS-7 cells, staurosporine-induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage coincided with increased eNOS degradation and decreased activity. Loss of eNOS activity was greater than the degree of proteolysis. Incubation of immunoprecipitated eNOS with caspase-3, caspase-6 or caspase-7 resulted in eNOS cleavage. Staurosporine, a general protein kinase inhibitor, also reduced phosphorylation and decreased calmodulin binding, an effect that may explain the reduction in activity. eNOS, therefore, is both an inhibitor of apoptosis and a target of apoptosis-associated proteolysis.

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“…Apoptotic signals initiated by a variety of stimuli converge on activation of a family of cysteine proteases, namely caspases (Dragovich et al, 1998;Thornberry and Lazebnik, 1998). Caspase activation results in proteolytic degradation of many proteins and ®nally causes apoptotic morphology.…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

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Overexpression of epidermal growth factor receptor (EGFR) and establishment of transforming growth factor a (TGF a)/EGF autocrine system are frequently detected in tumor cells. In addition to mitogenic ability, we demonstrate in this report that EGF protects a human esophageal carcinoma (CE) cell line, CE81T/VGH, from staurosporine-induced apoptosis. The anti-apoptotic signal of EGF is alleviated by a MEK inhibitor PK98059 or an ERK2 dominant negative mutant but not by a phosphatidylinositol-3'-kinase (PI-3K) inhibitor wortmannin. Furthermore, v-raf blocks apoptosis induced by staurosporine. This evidence implies that the survival signal of EGF is mediated via the Raf-MEK-ERK pathway but not the PI3-K pathway. The survival e ect of EGF is coincident with the induction of mcl-1, an antiapoptotic gene in the bcl-2 family. PD98059 also suppresses the induction of Mcl-1 by EGF, implying that EGF may up-regulate Mcl-1 via the MAP kinase pathway. Overexpression of mcl-1 is su cient to protect against apoptosis, while transfection of a mcl-1 antisense plasmid causes cell death. The expression of mcl-1 antisense plasmid also suppresses the anti-apoptotic e ect of EGF. Taken together, these results indicate that EGF may up-regulate Mcl-1 through the MAP kinase pathway to suppress apoptosis.

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Signal transduction pathways that regulate cell survival and cell death

Cited by 170 publications

References 36 publications

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

Effect of staurosporine-induced apoptosis on endothelial nitric oxide synthase in transfected COS-7 cells and primary endothelial cells

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

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