1. STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins.
- Author
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Rethi-Nagy, Zsuzsanna, Abraham, Edit, Udvardy, Katalin, Klement, Eva, Darula, Zsuzsanna, Pal, Margit, Katona, Robert L., Tubak, Vilmos, Pali, Tibor, Kota, Zoltan, Sinka, Rita, Udvardy, Andor, and Lipinszki, Zoltan
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CHIMERIC proteins , *RECOMBINANT proteins , *PROTEINS , *GENETIC transcription regulation , *DYNAMIC balance (Mechanics) , *PROTEASOMES - Abstract
The dynamic balance of transcriptional and translational regulation together with degron-controlled proteolysis shapes the ever-changing cellular proteome. While a large variety of degradation signals has been characterized, our knowledge of cis-acting protein motifs that can in vivo stabilize otherwise short-lived proteins is very limited. We have identified and characterized a conserved 13-mer protein segment derived from the p54/Rpn10 ubiquitin receptor subunit of the Drosophila 26S proteasome, which fulfills all the characteristics of a protein stabilization motif (STABILON). Attachment of STABILON to various intracellular as well as medically relevant secreted model proteins resulted in a significant increase in their cellular or extracellular concentration in mammalian cells. We demonstrate that STABILON acts as a universal and dual function motif that, on the one hand, increases the concentration of the corresponding mRNAs and, on the other hand, prevents the degradation of short-lived fusion proteins. Therefore, STABILON may lead to a breakthrough in biomedical recombinant protein production. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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