STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins
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 <i>cis</i>-acting protein motifs that can in v...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/15/8168 |
| _version_ | 1797413777505779712 |
|---|---|
| author | Zsuzsanna Rethi-Nagy Edit Abraham Katalin Udvardy Eva Klement Zsuzsanna Darula Margit Pal Robert L. Katona Vilmos Tubak Tibor Pali Zoltan Kota Rita Sinka Andor Udvardy Zoltan Lipinszki |
| author_facet | Zsuzsanna Rethi-Nagy Edit Abraham Katalin Udvardy Eva Klement Zsuzsanna Darula Margit Pal Robert L. Katona Vilmos Tubak Tibor Pali Zoltan Kota Rita Sinka Andor Udvardy Zoltan Lipinszki |
| author_sort | Zsuzsanna Rethi-Nagy |
| collection | DOAJ |
| description | 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 <i>cis</i>-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 <i>Drosophila</i> 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. |
| first_indexed | 2024-03-09T05:23:15Z |
| format | Article |
| id | doaj.art-6e38a211cb87403691e511379a50a12c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:23:15Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6e38a211cb87403691e511379a50a12c2023-12-03T12:38:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315816810.3390/ijms23158168STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted ProteinsZsuzsanna Rethi-Nagy0Edit Abraham1Katalin Udvardy2Eva Klement3Zsuzsanna Darula4Margit Pal5Robert L. Katona6Vilmos Tubak7Tibor Pali8Zoltan Kota9Rita Sinka10Andor Udvardy11Zoltan Lipinszki12Biological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungarySingle Cell Omics Advanced Core Facility, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), H-6726 Szeged, HungarySingle Cell Omics Advanced Core Facility, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), H-6726 Szeged, HungaryBiological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungaryINPAMAC Zrt, H-6723 Szeged, HungaryCreative Laboratory Ltd., H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, ELKH, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, ELKH, H-6726 Szeged, HungaryDepartment of Genetics, University of Szeged, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biochemistry, MTA SZBK Lendület Laboratory of Cell Cycle Regulation, ELKH, H-6726 Szeged, HungaryThe 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 <i>cis</i>-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 <i>Drosophila</i> 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.https://www.mdpi.com/1422-0067/23/15/8168stabilization motifprotein degradationprotein productionsecreted proteinsenhancermRNA stability |
| spellingShingle | Zsuzsanna Rethi-Nagy Edit Abraham Katalin Udvardy Eva Klement Zsuzsanna Darula Margit Pal Robert L. Katona Vilmos Tubak Tibor Pali Zoltan Kota Rita Sinka Andor Udvardy Zoltan Lipinszki STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins International Journal of Molecular Sciences stabilization motif protein degradation protein production secreted proteins enhancer mRNA stability |
| title | STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins |
| title_full | STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins |
| title_fullStr | STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins |
| title_full_unstemmed | STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins |
| title_short | STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins |
| title_sort | stabilon a novel sequence motif that enhances the expression and accumulation of intracellular and secreted proteins |
| topic | stabilization motif protein degradation protein production secreted proteins enhancer mRNA stability |
| url | https://www.mdpi.com/1422-0067/23/15/8168 |
| work_keys_str_mv | AT zsuzsannarethinagy stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT editabraham stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT katalinudvardy stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT evaklement stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT zsuzsannadarula stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT margitpal stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT robertlkatona stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT vilmostubak stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT tiborpali stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT zoltankota stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT ritasinka stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT andorudvardy stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins AT zoltanlipinszki stabilonanovelsequencemotifthatenhancestheexpressionandaccumulationofintracellularandsecretedproteins |