A5063517445- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- RNA modifications and cancer
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- NF-κB Signaling Pathways
- Cancer-related Molecular Pathways
- Cannabis and Cannabinoid Research
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Lysosomal Storage Disorders Research
- Mosquito-borne diseases and control
- Peptidase Inhibition and Analysis
- 14-3-3 protein interactions
- Signaling Pathways in Disease
Weizmann Institute of Science
2014-2024
Albert Einstein College of Medicine
1997-2002
Northwestern University
1999
University Medical Center
1999
Death-associated protein kinase (DAPk) and DAPk-related (DRP)-1 proteins are Ca+2/calmodulin–regulated Ser/Thr death kinases whose precise roles in programmed cell still mostly unknown. In this study, we dissected the subcellular events which these involved during death. Expression of each DAPk subfamily members their activated forms triggered two major cytoplasmic events: membrane blebbing, characteristic several types death, extensive autophagy, is typical autophagic (type II) These...
Significant numbers of myocytes die by apoptosis during myocardial infarction. The molecular mechanism this process, however, remains largely unexplored. To facilitate a genetic analysis, we have developed model ischemia-induced cardiac myocyte in the mouse. Surgical occlusion left coronary artery results apoptosis, as indicated presence nucleosome ladders and situ DNA strand breaks. Apoptosis occurs mainly myocytes, is shown for first time to be limited hypoxic regions acute Since...
Abstract —Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling was undertaken in primary cultures cardiac myocytes, a type especially sensitive ischemia-induced apoptosis. Deprivation serum glucose, components ischemia vivo, resulted myocyte apoptosis, as determined by nuclear fragmentation, internucleosomal cleavage DNA, processing...
Toxins convert the hepatocellular response to tumor necrosis factor-α (TNF-α) stimulation from proliferation cell death, suggesting that hepatotoxins somehow sensitize hepatocytes TNF-α toxicity. Because nuclear factor-κB (NF-κB) activation confers resistance cytotoxicity in nonhepatic cells, possibility toxin-induced sensitization killing results inhibition of NF-κB-dependent gene expression was examined RALA rat hepatocyte line sensitized by actinomycin D (ActD). ActD did not affect...
Death-associated protein kinase is a calcium/calmodulin serine/threonine kinase, which positively mediates programmed cell death in variety of systems. Here we addressed its mode regulation and identified mechanism that restrains apoptotic function growing cells enables activation during death. It involves autophosphorylation Ser<sup>308</sup>within the calmodulin (CaM)-regulatory domain, occurs at basal state, absence Ca<sup>2+</sup>/CaM, inversely correlated with substrate phosphorylation....
The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize allow retrieval pathway information in a way will be useful research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/ ) is database achieving this goal, containing highly curated interactions particular human pathways, along with literature-referenced nature each...
Activating alternative cell death pathways, including autophagic death, is a promising direction to overcome the apoptosis resistance observed in various cancers. Yet, whether autophagy acts as mechanism by over consumption of intracellular components still controversial and remains undefined at ultrastructural mechanistic levels. Here we identified conditions under which resveratrol-treated A549 lung cancer cells die that fulfills previous definition death. The displayed strong sustained...
The death-associated protein (DAP) kinase family includes three kinases, DAP kinase, kinaserelated 1, and ZIP which display 80% amino acid identity within their catalytic domains are functionally linked to common subcellular changes occurring during cell death, such as the process of membrane blebbing.Here we show physical functional cross talk between kinase.The two kinases strong synergistic effects on death when coexpressed physically bind each other via domains.Furthermore,...
Autophagy is a tightly regulated catabolic process, which upregulated in cells response to many different stress signals. Inhibition of mammalian target rapmaycin complex 1 (mTORC1) crucial step induction autophagy, yet the mechanisms regulating fine tuning its activity are not fully understood. Here we show that death-associated protein kinase 2 (DAPK2), Ca2+-regulated serine/threonine kinase, directly interacts with and phosphorylates mTORC1, has part suppressing mTOR promote autophagy...
Multiple transcriptional and epigenetic changes drive differentiation of embryonic stem cells (ESCs). This study unveils an additional level gene expression regulation involving noncanonical, cap-independent translation a select group mRNAs. is driven by death-associated protein 5 (DAP5/eIF4G2/NAT1), initiation factor mediating IRES-dependent translation. We found that the DAP5 knockdown from human ESCs (hESCs) resulted in persistence pluripotent expression, delayed induction...
Death associated protein 5 (DAP5/eIF4G2/NAT1) is a member of the eIF4G translation initiation factors that has been shown to mediate noncanonical and/or cap-independent translation. It essential for embryonic development and differentiation stem cells (ESCs), specifically its ability drive specific target mRNAs. In order expand repertoire DAP5 mRNAs, we compared ribosome profiles in control knockdown (KD) human ESCs (hESCs) identify mRNAs with decreased ribosomal occupancy upon silencing. A...