The process of autophagy, or lysosome-mediated degradation of damaged proteins and organelles in the cytosol, is a vital cellular process that acts as a quality control mechanism for proteins and organelles. The misregulation of autophagy can lead to an imbalance of cellular homeostasis and the subsequent development of disease. Therefore, the study of autophagy is at the forefront of neuroscience and cancer research, among others.
Eukaryotic translation initiation factor 4E binding protein 1, or 4EBP1, is an mRNA translational repressor protein that negatively regulates eukaryotic translation initiation factor 4E, or EIF4E. EIF4E is a protein that forms a complex necessary to block the 5’ ends of mRNA with a 7-methyl-guanosine five-prime cap structure, which is important for normal translation of mRNA. Specifically, the EIF4E complex recruits 40s ribosome subunits to scan mRNA in order to regulate protein synthesis. When EIF4E is bound to 4EBP1, it is held in an
HIF-2 alpha, also known as hypoxia-inducible factor 2, endothelial PAS domain protein-1, and member of PAS superfamily 2 is part of the HIF family of proteins. The HIF family is composed of HIF-1, HIF-2 and HIF-3, where HIF-2 is a dimeric protein that consists of an alpha and beta subunit.HIF-2 alphais activated in the presence of oxygen deprivation, or hypoxia, via prolyl hydroxylase-domain enzymes (PHD
The IKK complex, or inhibitor of NFkB kinase, is composed of IKK alpha and IKK beta. These kinases are at the core of the NFkB signaling cascade. The NFkB family is made up of transcription factors that are kept inactive in the cytoplasm through inhibitory IkB proteins.
AMP-activated protein kinase (AMPK) is best known as a sensor of oxidative stress. AMPK is activated by increased intracellular AMP levels, which are a result of alterations in cellular metabolism from causes such as hypoxia, changes in ATP, senescence and more. In cell stress models, AMPK can protect cells from reduced ATP production by altering ATP biosynthetic pathways. Furthermore, AMPK has implications in reducing inflammatory reactions in apoptosis pathways.