Mitochondrial p32 Is a Critical Mediator of ARF-Induced Apoptosis

kavin submitted, created time 3 months 2 weeks (www.cancercell.org)

The shared exon 2 of the p14ARF-p16INK4a locus is frequently mutated in human cancers. However, in contrast to the exon 1β-encoded N-terminal half of ARF, the function of the exon 2-encoded C-terminal half of ARF has been elusive. The authors report that the mitochondrial protein p32/C1QBP binds the ARF C terminus. They show that p32 is required for ARF to localize to mitochondria and induce apoptosis, and that ARF mutations specifically disrupting p32 binding can impair both of these functions

Submit comment | Blog It | Email It | Keywords: mitochondria Mitochondrial p32 apoptosis cell death human mitochondrial diseases ARF

ETosis: A Novel Cell Death Pathway

jerry submitted, created time 4 months 4 days (stke.sciencemag.org)

The formation of extracellular traps (ETs) by neutrophils and mast cells is an important mechanism in the innate immune response. These structures consist of a chromatin-DNA backbone with attached antimicrobial peptides and enzymes that trap and kill microbes. After stimulation of neutrophils and mast cells with phorbol esters, chemoattractant peptides, or chemokines, the generation of reactive oxygen species (ROS), such as hydrogen peroxide, by NAPDH oxidase initiates a signaling cascade that leads to the disintegration of the nuclear and cellular membranes and the formation of ETs

Submit comment | Blog It | Email It | Keywords: leukocytes necrosis neutrophils apoptosis ETosis Cell death

Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity

jerry submitted, created time 4 months 1 week (www.cancercell.org)

Expression of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase associated with cell proliferation and survival, is overactive in many tumors of epithelial origin. Blockade of the kinase activity of EGFR has been used for cancer therapy; however, by itself, it does not seem to reach maximum therapeutic efficacy. We report here that in human cancer cells, the function of kinase-independent EGFR is to prevent autophagic cell death by maintaining intracellular glucose level through interaction and stabilization of the sodium/glucose cotransporter 1 (SGLT1).

Submit comment | Blog It | Email It | Keywords: tyrosine kinase SGLT1 kinases apoptosis cancer EGFR epidermal growth factor receptor cancer cells

Dying on cue

sea-maid submitted, created time 4 months 1 week (www.jcb.org)

Earnshaw's group was hoping to crack a different question: how the cell's chromatin condenses during mitosis. In order to find the answer, they allowed researchers to create synchronized systems to study how protein-slicing enzymes such as the caspases orchestrate apoptosis.

3 comments | Blog It | Email It | Keywords: mitosis caspases chromatin DNA nuclei apoptosis

Hormone blocks opiate damage

sea-maid submitted, created time 4 months 1 week (www.pnas.org)

Previous studies have shown that chronic opiates may inhibit cell growth and trigger apoptosis leading to impaired cognitive capabilities in both humans and other mammals. And these results suggest that the hormone is capable of preventing or even repairing morphine-induced damage to hippocampal cells

4 comments | Blog It | Email It | Keywords: drugs brain damage opium opiates hippocampus morphine apoptosis cognition hormones hippocampal cells morphine-induced damage

Dynamics of RASSF1A/MOAP-1 Association with Death Receptors

kavin submitted, created time 4 months 2 weeks (www.ncbi.nlm.nih.gov)

RASSF1A associated with the TNF-R1/MOAP-1 or TRAIL-R1/MOAP-1 complex via its N-terminal cysteine-rich (C1) domain containing a potential zinc finger binding motif. Importantly, TNF-R1 association domains on both MOAP-1 and RASSF1A were essential for death receptor-dependent apoptosis. The association of RASSF1A and MOAP-1 with death receptors involves an ordered recruitment to receptor complexes to promote cell death and inhibit tumor formation.

1 comment | Blog It | Email It | Keywords: RASSF1A tumors apoptosis MOAP-1 TRAIL-R1 Death Receptors RASSF1A&MOAP-1

Met Tyrosine Kinase Deleted in Liver Progenitor Oval Cells Increases Sensitivity to Apoptosis in Vitro

p53 Activation: A Case against Sir

jerry submitted, created time 4 months 3 weeks (www.cancercell.org)

The p53 tumor suppressor is a critical transcription factor for controlling cell growth and apoptosis during times of cellular stress.

In this issue, the researchers screened small-molecule activators of p53 that could potentially reduce tumor growth Tenovin-6 was identified as a potent SIRT1 and SIRT2 inhibitor that indirectly activated p53 at single-digit micromolar concentrations.

The identification of a specific sirtuin inhibitor has broad implications in understanding sirtuin-p53 signaling and the development of novel chemotherapeutics

2 comments | Blog It | Email It | Keywords: p53-dependent apoptosis tumor growth apoptosis p53

Irradiation-Induced Proapoptotic Gene Expression is Controled by the Differentiation in Drosophila Embryos

When cells make a meal of themselves

Apoptosis: Killing neutrophils the cathepsin way

davidd submitted, created time 5 months 1 week (www.signaling-gateway.org)

Cathepsin D directly cleaves and activates caspase-8 at the beginning of a pro-apoptotic pathway in neutrophils, showing how apoptosis can be activated in the absence of death-receptor ligation.

2 comments | Blog It | Email It | Keywords: cell biology cell signaling neutrophils cell death cathepsin D caspase-8 apoptosis

From sequence to function: using RNAi to elucidate mechanisms of human disease

davidd submitted, created time 5 months 3 weeks (www.nature.com)

RNA interference (RNAi) has emerged as one of the most powerful tools for functionally characterizing large sets of genomic data. The capabilities of RNAi place it at the forefront of high-throughput screens, which are able to span the human genome in search of novel targets. The article assess the prospective applications of high-throughput screens, the data they are capable of generating, and the potential for this technique to further our understanding of human disease.

1 comment | Blog It | Email It | Keywords: RNA interference high-throughput screens drug targets therapeutic targets siRNA design apoptosis RNAi

Bcl-2-Regulated Calcium Signals as Common Mediators of Both Apoptosis and Autophagy

Vincent submitted, created time 6 months 3 weeks (www.sciencedirect.com)

Macroautophagy is an evolutionary conserved lysosomal pathway involved in the turnover of cellular macromolecules and organelles. In spite of its essential role in tissue homeostasis, the molecular mechanisms regulating mammalian macroautophagy are poorly understood. Here, we demonstrate that a rise in the free cytosolic calcium ([Ca2+]c) is a potent inducer of macroautophagy

Submit comment | Blog It | Email It | Keywords: lysosomes cell signaling autophagy apoptosis calcium Ca2+ sensors

Cell death by necrosis: towards a molecular definition

Vincent submitted, created time 6 months 3 weeks (images.cell.com)

Necrosis has been defined as a type of cell death that
lacks the features of apoptosis and autophagy, and is
usually considered to be uncontrolled. Recent research
suggests, however, that its occurrence and course might
be tightly regulated. After signaling- or damage-induced
lesions, necrosis can include signs of controlled processes
such as mitochondrial dysfunction, enhanced
generation of reactive oxygen species, ATP depletion,
proteolysis by calpains and cathepsins, and early plasma
membrane rupture

3 comments | Blog It | Email It | Keywords: apoptosis cancer tumors necrosis

MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Stomach Cancer

davidd submitted, created time 6 months 3 weeks (www.cancercell.org)

Stomach cancer causes 12% of all cancer-related deaths each year, a fact that calls for better treatments based on a deeper understanding of the molecular mechanisms underlying the onset of this disease. Here, they show that overexpression of the miR-106b-25 cluster may cure the TGFβ tumor suppressor pathway related cancer.

1 comment | Blog It | Email It | Keywords: diagnoses tumors apoptosis diagnosis molecular diagnosis miRNA cancer