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.
