Good news! Cancer is history (soon)! P53 is reported to help to explain longevity in elephants and why elephants are less prone to cancer (see my blog post).
"... The team used gene editing techniques to combine the gene for p53 with a sequence encoding the spider silk protein’s lengthy N-terminal domain and inserted the product into a bacterial plasmid. ...
human cells produced the hybrid protein 10 times more efficiently than they did p53, and the hybrid was considerably more stable. In subsequent experiments ... the protein was also more efficient at killing lab-grown tumors. ..."
human cells produced the hybrid protein 10 times more efficiently than they did p53, and the hybrid was considerably more stable. In subsequent experiments ... the protein was also more efficient at killing lab-grown tumors. ..."
From the abstract:
"Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of “life on the edge of solubility.” Here, we investigate whether these features can be modulated by fusing the protein to a highly soluble spider silk domain (NT∗). The chimeric protein displays highly efficient translation and is fully active in human cancer cells. Biophysical characterization reveals a compact conformation, with the disordered transactivation domain of p53 wrapped around the NT∗ domain. We conclude that interactions with NT∗ help to unblock translation of the proline-rich disordered region of p53. Expression of partially disordered cancer targets is similarly enhanced by NT∗. In summary, we demonstrate that inducing co-translational folding via a molecular “spindle and thread” mechanism unblocks protein translation in vitro."
A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder (open access)
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