PubMed · 14283758
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J S SCOTT, A D BAIN. 1965-05-15. GASTRIN.. https://pubmed.ncbi.nlm.nih.gov/14283758/
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Cytosolic internalization is a requirement for the toxicity of secretory ribonucleases. Here, we investigate the mechanism of internalization of Onconase (ONC), a toxic protein, and ribonuclease A (RNase A), a nontoxic homolog. Microscopy studies indicate that both ribonucleases readily bind to the cell surface and are internalized via acidic vesicles. Blocking dynamin-dependent endocytosis prevents transferrin internalization but does not hinder RNase A internalization. ONC and G88R RNase A, which is a toxic variant, demonstrate enhanced cytotoxicity in the absence of clathrin- and dynamin-mediated endocytosis. The cytosolic entry of ribonucleases does not require an acidic environment or transport to the ER and probably occurs from endosomes. Thus, common proteins - secretory ribonucleases - enter the cytosol by a pathway that is distinct from that of other known toxins.
The overexpression of certain membrane proteins is accompanied by a striking proliferation of intracellular membranes. One of the best characterized inducers of membrane proliferation is the 180-kD mammalian ribosome receptor (p180), whose expression in yeast results in increases in levels of mRNAs encoding proteins that function in the secretory pathway, and an elevation in the cell's ability to secrete proteins. In this study we demonstrate that neither the unfolded protein response nor increased transcription accounts for membrane proliferation or the observed increase in secretory pathway mRNAs. Rather, p180-induced up-regulation of certain secretory pathway transcripts is due to a p180-mediated increase in the longevity of these mRNA species, as determined by measurements of transcriptional activity and specific mRNA turnover. Moreover, we show that the longevity of mRNA in general is substantially promoted through the process of its targeting to the membrane of the endoplasmic reticulum. With respect to the terminal differentiation of secretory tissues, results from this model system provide insights into how the expression of a single protein, p180, could result in substantial morphological and functional changes.
Are ethical and political questions discussed more in aesthetic than in social terms? Political debates in contemporary art are often expressed through the use of symbolic power structures that are related to bodily secretions and products. By visualizing the less delicate parts of the organic body, contemporary artists focus on the vulnerability of the human body and its illness and pain. If human suffering is aestheticized: is this a question of form or a question of creating a cultural cover-up? Bodily secretions are associated with a range of complex social and cultural meanings and symbols. Metaphors related to body products may function as markers of ethnic, religious, social and sexual differences. In postmodern cultural criticism, the symbolic power of body metaphors is of great importance.