Adaptation of Proteasomes and Lysosomes to Cellular Environments

Abstract

Protein degradation is important for proper cellular physiology as it removes malfunctioning proteins or can provide a source for energy. Proteasomes and lysosomes, through the regulatory particles or adaptor proteins, respectively, recognize proteins destined for degradation. These systems have developed mechanisms to allow adaptation to the everchanging environment of the cell. While the complex recognition of proteins to be degraded is somewhat understood, the mechanisms that help switch the proteasomal regulatory particles or lysosomal adaptor proteins to adjust to the changing landscape of degrons, during infections or inflammation, still need extensive exploration. Therefore, this review is focused on describing the protein degradation systems and the possible sensors that may trigger the rapid adaptation of the protein degradation machinery.

Targeted Protein Degradation through Fast Optogenetic Activation and Its Application to the Control of Cell Signaling

“…Loss of fluorescence in cells expressing lower initial EGFP fluorescence was rapid, reaching near complete degradation immediately upon the second irradiation at 10 min. These results revealed an inverse correlation between initial POI levels and degradation efficiency, presumably due to oversaturation of the proteasomal machinery. − This correlation is consistent with the increased level of protein degradation observed in translationally inhibited cells after 24 h, compared to a shorter (30 min) degradation period. POI levels suitable for rapid degradation via optoDeg should be readily achievable through simple concentration adjustments of HCK, which directly impacts protein expression levels …”

“…Cells displaying only up to 33% decrease in EGFP fluorescence upon decaging express on average 70% more EGFP prior to irradiation than cells reaching near complete degradation of optoDeg-EGFP. This supports the hypothesis that increased protein expression can overwhelm N-end pathway machinery, ultimately decreasing proteolytic efficiency after acute activation. − …”

Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells

“…Our data regarding the intracellular and organelle distribution of VEGFR1/2 following VEGF activation indicates that: (1) C-terminal VEGFR1 nuclear translocation was not significantly impacted by blockade of receptor synthesis even though reduced localization of VEGFR1 was observed in the Golgi complex suggesting that VEGFR1 translocates to the nucleus from trans Golgi apparatus and early endosomes, probably leaving via the recycling pathway; (2) VEGFR2 nuclear translocation was minimal when the biosynthetic pool was inhibited and together with the strong temporal and spatial association with early endosomes indicates that VEGFR2 derives from Golgi after rapid biosynthesis and translocates to the nucleus via the early endosome-mediated pathway; and (3) post-signaling reduction of nuclear VEGFRs suggests that they can exit the nucleus and probably reenter the endosomal pathway for degradation as we see an increase co-localization of VEGFRs with lysosomes. It is well recognized that nuclear proteins are exported from the nucleus and can enter the proteosomal and lysosomal pathways and that there is significant interplay between these two pathways 47 , 48 . Molecular studies are needed to determine the mechanism(s) by which VEGFRs enter and exit the nucleus since they do not contain a nuclear localization/export signal.…”

Long Noncoding RNA: A Novel Insight into the Pathogenesis of Acute Lung Injury

“…However, more than 50% of the expressed lncRNAs are found in the cytoplasm, while the nucleus also possesses a high concentration of lncRNAs. LncRNAs can promote protein degradation, a crucial process for the maintenance of cellular physiology [ 78 ]. Both the major pathways of protein degradation, the ubiquitin–proteasome system, and the autophagy–lysosome system [ 78 ], can enhance protein degradation with the help of lncRNAs.…”

“…LncRNAs can promote protein degradation, a crucial process for the maintenance of cellular physiology [ 78 ]. Both the major pathways of protein degradation, the ubiquitin–proteasome system, and the autophagy–lysosome system [ 78 ], can enhance protein degradation with the help of lncRNAs. LncRNAs can also contribute to the mRNA and protein content of the cell by regulating the expression of the flanking protein-coding genes.…”