scholarly journals Targeted Destruction of DNA Replication Protein Cdc6 by Cell Death Pathways in Mammals and Yeast

2002 ◽  
Vol 13 (5) ◽  
pp. 1536-1549 ◽  
Author(s):  
Frederic Blanchard ◽  
Michael E. Rusiniak ◽  
Karuna Sharma ◽  
Xiaolei Sun ◽  
Ivan Todorov ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Replication ◽  
Extrinsic Pathway ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cell Death Pathways ◽  
Programmed Death ◽  
Eukaryotic Dna ◽  
Factor Α ◽  
Dependent Pathway ◽  
Necrosis Factor

The highly conserved Cdc6 protein is required for initiation of eukaryotic DNA replication and, in yeast and Xenopus, for the coupling of DNA replication to mitosis. Herein, we show that human Cdc6 is rapidly destroyed by a p53-independent, proteasome-, and ubiquitin-dependent pathway during early stages of programmed cell death induced by the DNA-damaging drug adozelesin, or by a separate caspase-dependent pathway in cells undergoing apoptosis through an extrinsic pathway induced by tumor necrosis factor-α and cycloheximide. The proteasome-dependent pathway induced by adozelesin is conserved in the budding yeast Saccharomyces cerevisiae. The destruction of Cdc6 may be a primordial programmed death response that uncouples DNA replication from the cell division cycle, which is reinforced in metazoans by the evolution of caspases and p53.

scholarly journals The role of Ubiquitination in Apoptosis and Necroptosis

2021 ◽  
Author(s):  
Jamie Z. Roberts ◽  
Nyree Crawford ◽  
Daniel B. Longley
Keyword(s):  
Cell Death ◽  
Death Receptors ◽  
Tnf Receptor ◽  
Extrinsic Pathway ◽  
Post Translational Modifications ◽  
Cell Death Pathways ◽  
Apoptotic Pathways ◽  
Extrinsic Apoptotic Pathways ◽  
Necrosis Factor

AbstractCell death pathways have evolved to maintain tissue homoeostasis and eliminate potentially harmful cells from within an organism, such as cells with damaged DNA that could lead to cancer. Apoptosis, known to eliminate cells in a predominantly non-inflammatory manner, is controlled by two main branches, the intrinsic and extrinsic apoptotic pathways. While the intrinsic pathway is regulated by the Bcl-2 family members, the extrinsic pathway is controlled by the Death receptors, members of the tumour necrosis factor (TNF) receptor superfamily. Death receptors can also activate a pro-inflammatory type of cell death, necroptosis, when Caspase-8 is inhibited. Apoptotic pathways are known to be tightly regulated by post-translational modifications, especially by ubiquitination. This review discusses research on ubiquitination-mediated regulation of apoptotic signalling. Additionally, the emerging importance of ubiquitination in regulating necroptosis is discussed.

scholarly journals Tumor Necrosis Factor-α-Activated Cell Death Pathways in NIT-1 Insulinoma Cells and Primary Pancreatic β Cells*

Endocrinology ◽  
1999 ◽  
Vol 140 (7) ◽  
pp. 3219-3227 ◽  
Author(s):  
Leigh A. Stephens ◽  
Helen E. Thomas ◽  
Li Ming ◽  
Matthias Grell RIMA DARWICHE ◽  
Leonid Volodin ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cell Death Pathways ◽  
Insulinoma Cells ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production

2021 ◽  
Author(s):  
Yan Liang ◽  
Xiaoli Sun ◽  
Mingjie Wang ◽  
Qingmiao Lu ◽  
Mengru Gu ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Cell ◽  
Kidney Fibrosis ◽  
Tubular Cells ◽  
Ureter Obstruction ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Rap1 Activation ◽  
Necrosis Factor ◽  
Macrophage Accumulation

AbstractMacrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα−/− macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

scholarly journals Tumor Necrosis Factor-α Increases ATP Content in Metabolically Inhibited L929 Cells Preceding Cell Death

1997 ◽  
Vol 272 (48) ◽  
pp. 30167-30177 ◽  
Author(s):  
José A. Sánchez-Alcázar ◽  
Jesús Ruı́z-Cabello ◽  
Inmaculada Hernández-Muñoz ◽  
Pilar Sánchez Pobre ◽  
Paz de la Torre ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Atp Content ◽  
L929 Cells ◽  
Factor Α ◽  
Necrosis Factor ◽  
Preceding Cell

scholarly journals DNA REPLICATION ARREST AND P53-DEPENDENT AND P53-INDEPENDENT CELL DEATH PATHWAYS IN XERODERMA PIGMENTOSUM VARIANT CELLS

2001 ◽  
Vol 1 (S3) ◽  
pp. 60-60
Author(s):  
James E. Cleaver ◽  
Eileen Crowley ◽  
Mohammed Kashani-Sabet ◽  
Charles L. Limoli
Keyword(s):  
Cell Death ◽  
Dna Replication ◽  
Xeroderma Pigmentosum ◽  
Replication Arrest ◽  
Cell Death Pathways

Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-α

2002 ◽  
Vol 282 (2) ◽  
pp. G257-G266 ◽  
Author(s):  
Hailing Liu ◽  
Brett E. Jones ◽  
Cynthia Bradham ◽  
Mark J. Czaja
Keyword(s):  
Cell Death ◽  
Oxidant Stress ◽  
Nuclear Factor Κb ◽  
Dominant Negative ◽  
Tnf Α ◽  
Cyp2e1 Expression ◽  
Factor Α ◽  
Jnk Activation ◽  
Cytochrome P 450 ◽  
Necrosis Factor

The mechanisms underlying hepatocyte sensitization to tumor necrosis factor-α (TNF-α)-mediated cell death remain unclear. Increases in hepatocellular oxidant stress such as those that occur with hepatic overexpression of cytochrome P-450 2E1 (CYP2E1) may promote TNF-α death. TNF-α treatment of hepatocyte cell lines with differential CYP2E1 expression demonstrated that overexpression of CYP2E1 converted the hepatocyte TNF-α response from proliferation to apoptotic and necrotic cell death. Death occurred despite the presence of increased levels of nuclear factor-κB transcriptional activity and was associated with increased lipid peroxidation and GSH depletion. CYP2E1-overexpressing hepatocytes had increased basal and TNF-α-induced levels of c-Jun NH2-terminal kinase (JNK) activity, as well as prolonged JNK activation after TNF-α stimulation. Sensitization to TNF-α-induced cell death by CYP2E1 overexpression was inhibited by antioxidants or adenoviral expression of a dominant-negative c-Jun. Increased CYP2E1 expression sensitized hepatocytes to TNF-α toxicity mediated by c-Jun and overwhelming oxidative stress. The chronic increase in intracellular oxidant stress created by CYP2E1 overexpression may serve as a mechanism by which hepatocytes are sensitized to TNF-α toxicity in liver disease.

scholarly journals Yersinia enterocolitica Impairs Activation of Transcription Factor NF-κB: Involvement in the Induction of Programmed Cell Death and in the Suppression of the Macrophage Tumor Necrosis Factor α Production

1998 ◽  
Vol 187 (7) ◽  
pp. 1069-1079 ◽  
Author(s):  
Klaus Ruckdeschel ◽  
Suzanne Harb ◽  
Andreas Roggenkamp ◽  
Mathias Hornef ◽  
Robert Zumbihl ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Tumor Necrosis Factor ◽  
Programmed Cell Death ◽  
Proteasome Inhibitor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

In this study, we investigated the activity of transcription factor NF-κB in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-κB signal, Y. enterocolitica inhibited NF-κB activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IκB-α and IκB-β observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-κB and to suppress the tumor necrosis factor α (TNF-α) production as well as to trigger macrophage apoptosis. When NF-κB activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF-α secretion. Y. enterocolitica also impaired the activity of NF-κB in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-α could induce HeLa cell apoptosis alone, TNF-α provoked apoptosis when activation of NF-κB was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-κB, which inhibits TNF-α release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

Mitochondrial dynamics in yeast cell death and aging

2011 ◽  
Vol 39 (5) ◽  
pp. 1520-1526 ◽  
Author(s):  
Ralf J. Braun ◽  
Benedikt Westermann
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Dynamics ◽  
Progressive Increase ◽  
Mitochondrial Morphology ◽  
Aging Research ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cell Death Pathways ◽  
Dependent Cell ◽  
Mitochondrial Networks

Mitochondria play crucial roles in programmed cell death and aging. Different stimuli activate distinct mitochondrion-dependent cell death pathways, and aging is associated with a progressive increase in mitochondrial damage, culminating in oxidative stress and cellular dysfunction. Mitochondria are highly dynamic organelles that constantly fuse and divide, forming either interconnected mitochondrial networks or separated fragmented mitochondria. These processes are believed to provide a mitochondrial quality control system and enable an effective adaptation of the mitochondrial compartment to the metabolic needs of the cell. The baker's yeast, Saccharomyces cerevisiae, is an established model for programmed cell death and aging research. The present review summarizes how mitochondrial morphology is altered on induction of cell death or on aging and how this correlates with the induction of different cell death pathways in yeast. We highlight the roles of the components of the mitochondrial fusion and fission machinery that affect and regulate cell death and aging.

Sign in / Sign up

Export Citation Format

Share Document