Evidence map›Paper›PMID 35260576›Full record

ArticleNature communications2022

Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage.

Arne Praznik, Tina Fink, Nik Franko, Jan Lonzarić, Mojca Benčina, Nina Jerala, Tjaša Plaper, Samo Roškar, Roman Jerala

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024
    Article
  17. Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024
    Review
  18. Article
  19. Orthogonalized human protease control of secreted signals.bioRxiv : the preprint server for biology · 2024
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Arne PraznikDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Tina FinkDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Nik FrankoDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0001-5256-2134
Jan LonzarićDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Mojca BenčinaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0002-3644-9948
Nina JeralaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Tjaša PlaperDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
Samo RoškarDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0002-3314-0339
Roman JeralaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia. roman.jerala@ki.si.ORCID http://orcid.org/0000-0002-6337-5251
National Institute of Chemistry · SIUniversity of Ljubljana · SIEN-FIST Centre of Excellence (Slovenia) · SI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Secreted proteins, such as hormones or cytokines, are key mediators in multicellular organisms. Response of protein secretion based on transcriptional control is rather slow, as it requires transcription, translation and transport from the endoplasmic reticulum (ER) to the plasma membrane via the conventional protein secretion (CPS) pathway. An alternative regulation to provide faster response would be valuable. Here we present two genetically encoded orthogonal regulatory secretion systems, which rely on the retention of pre-synthesized proteins on the ER membrane (membER, released by a cytosolic protease) or inside the ER lumen (lumER, released by an ER-luminal protease), respectively, and their release by the chemical signal-regulated proteolytic removal of an ER-retention signal, without triggering ER stress due to protein aggregates. Design of orthogonal chemically-regulated split proteases enables the combination of signals into logic functions. Its application was demonstrated on a chemically regulated therapeutic protein secretion and regulated membrane translocation of a chimeric antigen receptor (CAR) targeting cancer antigen. Regulation of the ER escape represents a platform for the design of fast-responsive and tightly-controlled modular and scalable protein secretion system for mammalian cells.

Indexed as

Endoplasmic ReticulumEndoplasmic Reticulum StressAnimalsEndopeptidasesMammalsPeptide HydrolasesProtein TransportProteolysisEndopeptidasesPeptide Hydrolases

Identifiers

PMID35260576
PMCPMC8904541
OpenAlexW4220866630

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.