scholarly journals Identification of the nuclear localisation signal of O-GlcNAc transferase and its nuclear import regulation

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hyeon Gyu Seo ◽  
Han Byeol Kim ◽  
Min Jueng Kang ◽  
Joo Hwan Ryum ◽  
Eugene C. Yi ◽  
...  
Keyword(s):  
Nuclear Import ◽  
Nuclear Localisation Signal ◽  
Nuclear Localisation ◽  
Glcnac Transferase

scholarly journals Targeted cell imaging properties of a deep red luminescent iridium(iii) complex conjugated with a c-Myc signal peptide

2020 ◽  
Vol 11 (6) ◽  
pp. 1599-1606 ◽  
Author(s):  
Adam H. Day ◽  
Martin H. Übler ◽  
Hannah L. Best ◽  
Emyr Lloyd-Evans ◽  
Robert J. Mart ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Cell Imaging ◽  
Organometallic Complex ◽  
Nuclear Localisation Signal ◽  
Nuclear Localisation ◽  
Imaging Properties

Visualising a c-Myc nuclear localisation signal peptide using an organometallic complex.

scholarly journals A functional bipartite nuclear localisation signal in the cytokine interleukin-5

FEBS Letters ◽  
1997 ◽  
Vol 406 (3) ◽  
pp. 315-320 ◽  
Author(s):  
David A. Jans ◽  
Lyndall J. Briggs ◽  
Sonja E. Gustin ◽  
Patricia Jans ◽  
Sally Ford ◽  
...  
Keyword(s):  
Nuclear Localisation Signal ◽  
Nuclear Localisation ◽  
Interleukin 5

scholarly journals Adenovirus Terminal Protein Contains a Bipartite Nuclear Localisation Signal Essential for Its Import into the Nucleus

2021 ◽  
Vol 22 (7) ◽  
pp. 3310
Author(s):  
Hareth A. Al-Wassiti ◽  
David R. Thomas ◽  
Kylie M. Wagstaff ◽  
Stewart A. Fabb ◽  
David A. Jans ◽  
...  
Keyword(s):  
Confocal Imaging ◽  
Nuclear Localisation Signal ◽  
Nuclear Entry ◽  
Terminal Protein ◽  
Nuclear Localisation ◽  
Host Interactions ◽  
Nuclear Uptake ◽  
Covalently Linked ◽  
Nuclear Shuttling ◽  
Future Work

Adenoviruses contain dsDNA covalently linked to a terminal protein (TP) at the 5′end. TP plays a pivotal role in replication and long-lasting infectivity. TP has been reported to contain a nuclear localisation signal (NLS) that facilitates its import into the nucleus. We studied the potential NLS motifs within TP using molecular and cellular biology techniques to identify the motifs needed for optimum nuclear import. We used confocal imaging microscopy to monitor the localisation and nuclear association of GFP fusion proteins. We identified two nuclear localisation signals, PV(R)6VP and MRRRR, that are essential for fully efficient TP nuclear entry in transfected cells. To study TP–host interactions further, we expressed TP in Escherichia coli (E. coli). Nuclear uptake of purified protein was determined in digitonin-permeabilised cells. The data confirmed that nuclear uptake of TP requires active transport using energy and shuttling factors. This mechanism of nuclear transport was confirmed when expressed TP was microinjected into living cells. Finally, we uncovered the nature of TP binding to host nuclear shuttling proteins, revealing selective binding to Imp β, and a complex of Imp α/β but not Imp α alone. TP translocation to the nucleus could be inhibited using selective inhibitors of importins. Our results show that the bipartite NLS is required for fully efficient TP entry into the nucleus and suggest that this translocation can be carried out by binding to Imp β or Imp α/β. This work forms the biochemical foundation for future work determining the involvement of TP in nuclear delivery of adenovirus DNA.

scholarly journals Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for…

2020 ◽  
Vol 48 (5) ◽  
pp. 1859-1875
Author(s):  
Simon J. Cook ◽  
Julie A. Tucker ◽  
Pamela A. Lochhead
Keyword(s):  
Protein Kinase ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Kinase Domain ◽  
Transactivation Domain ◽  
Nuclear Localisation Signal ◽  
Nuclear Localisation ◽  
Cancer And Inflammation

ERK5 is a protein kinase that also contains a nuclear localisation signal and a transcriptional transactivation domain. Inhibition of ERK5 has therapeutic potential in cancer and inflammation and this has prompted the development of ERK5 kinase inhibitors (ERK5i). However, few ERK5i programmes have taken account of the ERK5 transactivation domain. We have recently shown that the binding of small molecule ERK5i to the ERK5 kinase domain stimulates nuclear localisation and paradoxical activation of its transactivation domain. Other kinase inhibitors paradoxically activate their intended kinase target, in some cases leading to severe physiological consequences highlighting the importance of mitigating these effects. Here, we review the assays used to monitor ERK5 activities (kinase and transcriptional) in cells, the challenges faced in development of small molecule inhibitors to the ERK5 pathway, and classify the molecular mechanisms of paradoxical activation of protein kinases by kinase inhibitors.

Dynamic changes in nuclear import of a nuclear localisation signal-bearing substrate in 8-cell stage porcine embryos

2015 ◽  
Vol 27 (2) ◽  
pp. 385 ◽  
Author(s):  
Yanfang Li ◽  
Ki-Eun Park ◽  
Ryan A. Cabot
Keyword(s):  
Nuclear Import ◽  
In Vitro Assays ◽  
Cell Stage ◽  
Nuclear Trafficking ◽  
Nuclear Localisation ◽  
Cellular Events ◽  
Stage Of Development ◽  
Importin Α

Coordinated intracellular trafficking is critically important for proper timing of major cellular events during embryogenesis. Nuclear import mediated by the karyopherin α/β (importin α/β) heterodimer is perhaps the best characterised nuclear trafficking system in eukaryotic cells. Seven karyopherin α subtypes have been identified in the domestic pig, and although each karyopherin α subtype transports proteins bearing classical nuclear localisation signals (NLSs), individual karyopherin α subtypes have been shown to preferentially transport specific cargoes. The aim of the present study was to determine the mechanism by which BRN2, a transcription factor previously reported to be transported by the karyopherin α/β heterodimer, gains access to the nucleus in porcine oocytes and embryos. Using a combination of in vivo and in vitro assays, we tested the hypothesis that discrete karyopherin α subtypes transport BRN2 into the nuclei of porcine oocytes and cleavage stage embryos. Our results show that ectopically expressed BRN2 adopts a nuclear localisation in all nuclei through the 4-cell stage of development, whereas only a subset of blastomeres in 8-cell stage embryos possess nuclear BRN2. This pattern is unique to BRN2 because another ectopically expressed NLS-containing protein is able to adopt a nuclear localisation in all blastomeres of 8-cell stage embryos.

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