Back to Search
Start Over
Using a Simple Cellular Assay to Map NES Motifs in Cancer-Related Proteins, Gain Insight into CRM1-Mediated NES Export, and Search for NES-Harboring Micropeptides
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 17, Addi: Archivo Digital para la Docencia y la Investigación, Universidad del País Vasco, Addi. Archivo Digital para la Docencia y la Investigación, instname, International Journal of Molecular Sciences, Vol 21, Iss 6341, p 6341 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
Abstract
- The nuclear export receptor CRM1 (XPO1) recognizes and binds specific sequence motifs termed nuclear export signals (NESs) in cargo proteins. About 200 NES motifs have been identified, but over a thousand human proteins are potential CRM1 cargos, and most of their NESs remain to be identified. On the other hand, the interaction of NES peptides with the &ldquo<br />NES-binding groove&rdquo<br />of CRM1 was studied in detail using structural and biochemical analyses, but a better understanding of CRM1 function requires further investigation of how the results from these in vitro studies translate into actual NES export in a cellular context. Here we show that a simple cellular assay, based on a recently described reporter (SRVB/A), can be applied to identify novel potential NESs motifs, and to obtain relevant information on different aspects of CRM1-mediated NES export. Using cellular assays, we first map 19 new sequence motifs with nuclear export activity in 14 cancer-related proteins that are potential CRM1 cargos. Next, we investigate the effect of mutations in individual NES-binding groove residues, providing further insight into CRM1-mediated NES export. Finally, we extend the search for CRM1-dependent NESs to a recently uncovered, but potentially vast, set of small proteins called micropeptides. By doing so, we report the first NES-harboring human micropeptides.
- Subjects :
- 0301 basic medicine
viruses
Amino Acid Motifs
Receptors, Cytoplasmic and Nuclear
environment and public health
CRM1
lcsh:Chemistry
Genes, Reporter
Neoplasms
lcsh:QH301-705.5
Spectroscopy
nuclear export signal
cellular assay
General Medicine
Computer Science Applications
Neoplasm Proteins
micropeptide
XPO1
lipids (amino acids, peptides, and proteins)
nuclear export
Sequence motif
Active Transport, Cell Nucleus
Context (language use)
Computational biology
Biology
Karyopherins
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Humans
Physical and Theoretical Chemistry
Nuclear export signal
Molecular Biology
Human proteins
Nuclear Export Signals
030102 biochemistry & molecular biology
Cellular Assay
Organic Chemistry
fungi
Peptide Fragments
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Mutation
NES
Relevant information
Function (biology)
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences, Volume 21, Issue 17, Addi: Archivo Digital para la Docencia y la Investigación, Universidad del País Vasco, Addi. Archivo Digital para la Docencia y la Investigación, instname, International Journal of Molecular Sciences, Vol 21, Iss 6341, p 6341 (2020)
- Accession number :
- edsair.doi.dedup.....da9867bf0eb72b6881ff3238170f5bd2