Integrated Training in Cancer Model Systems
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1.Activation and Evasion of Innate Immunity by Gammaherpesviruses
- 关键词：
- KSHV; EBV; MHV68; gammaherpesvirus; innate immunity;EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED-HERPESVIRUS; NF-KAPPA-B;TOLL-LIKE RECEPTORS; PLASMACYTOID DENDRITIC CELLS; NATURAL-KILLER-CELLS;SINGLE-STRANDED RNA; RIG-I; INTERFERON-ALPHA; CUTTING EDGE
Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections in the vast majority of adults worldwide. Importantly, these viruses are associated with numerous malignancies and are respon-sible for significant human cancer burden. These virus-associated cancers are due, in part, to the ability of gammaherpesviruses to successfully evade the innate immune response throughout the course of infec-tion. In this review, we will summarize the current understanding of how gammaherpesviruses are detected by innate immune sensors, how these viruses evade recognition by host cells, and how this knowledge can inform novel therapeutic approaches for these viruses and their associated diseases. (c) 2021 Elsevier Ltd. All rights reserved.
...2.Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways
- 关键词：
- cell cycle; cell signaling; apoptosis; mitosis; chemotherapy; kinase;protein networks; DNA damage; cell stress;ACTIVATED PROTEIN-KINASE; OUTER-MEMBRANE PERMEABILIZATION; N-TERMINALPHOSPHORYLATION; DNA-DAMAGE; BCL-2 FAMILY; RETINOBLASTOMA PROTEIN;UP-REGULATION; P38-ALPHA MAPK; CDK INHIBITORS; BH3 DOMAINS
Protein signaling networks are formed from diverse and inter-connected cell signaling pathways converging into webs of function and regulation. These signaling pathways both receive and conduct molecular messages, often by a series of post-translation modifications such as phosphorylation or through protein-protein interactions via intrinsic motifs. The mitogen activated protein kinases (MAPKs) are components of kinase cascades that transmit signals through phosphorylation. There are several MAPK subfamilies, and one subfamily is the stress-activated protein kinases, which in mammals is the p38 family. The p38 enzymes mediate a variety of cellular outcomes including DNA repair, cell survival/cell fate decisions, and cell cycle arrest. The cell cycle is itself a signaling system that precisely controls DNA replication, chromosome segregation, and cellular division. Another indispensable cell function influenced by the p38 stress response is programmed cell death (apoptosis). As the regulators of cell survival, the BCL2 family of proteins and their dynamics are exquisitely sensitive to cell stress. The BCL2 family forms a protein-protein interaction network divided into anti-apoptotic and pro-apoptotic members, and the balance of binding between these two sides determines cell survival. Here, we discuss the intersections among the p38 MAPK, cell cycle, and apoptosis signaling pathways.
...3.Binge Drinking: Macropinocytosis Promotes Tumorigenic Growth of RAS-Mutant Cancers
- 关键词：
- PROTEIN
The RAS oncoprotein drives elevated macropinocytosis, a metabolic process essential for cancer growth. A recent study by Ramirez et al. elucidated a mechanism whereby RAS controls V-ATPase association-with the plasma membrane to drive RAC1 GTPase-dependent macropinocytosis. Potentially actionable targets to disrupt this RAS-dependent nutrient acquisition pathway were identified.
...4.Mitochondrial GSDMD Pores DAMPen Pyroptosis
- 关键词：
- UPSTREAM
Noncanoncial inflammasome activation by cytosolic lipopolysaccharide (LPS) causes pyroptotic cell death facilitated by gasdermin D (GSDMD) pore formation. In this issue of Immunity, Huang et al. describe how cytosolic LPS in endothelial cells does not cause cell death but restrains endothelial cell proliferation.
...5.Blocking autophagy to starve pancreatic cancer