scholarly journals The Nuclear Transport Protein Importin-5: A Promising Target in Oncology and Virology

2021 ◽  
Vol 75 (4) ◽  
pp. 319-322
Author(s):  
Rémi Patouret
Keyword(s):  
Nuclear Import ◽  
Protein Trafficking ◽  
Normal Function ◽  
Pivotal Role ◽  
Cellular Functions ◽  
Rna Molecules ◽  
Promising Target ◽  
Transport Receptors ◽  
Number Of Publications ◽  
Import Receptor

Cellular homeostasis importantly relies on the correct nucleoplasmic distribution of a large number of RNA molecules and proteins, which are shuttled by specialized transport receptors. The nuclear import receptor importin-5, also called IPO5, RanBP5 or karyopherin β3, mediates the translocation of proteins to the nucleus, and thus regulates critical signaling pathways and cellular functions. The normal function of IPO5 appears to be disrupted in cancer cells due to aberrant overexpression. IPO5 also demonstrated a pivotal role in viral replication. The constant increasing number of publications shows an interest within the scientific community as a therapeutic target due to its pivotal role in protein trafficking.

scholarly journals Nuclear import of histones

2020 ◽  
Vol 48 (6) ◽  
pp. 2753-2767
Author(s):  
Natalia Elisa Bernardes ◽  
Yuh Min Chook
Keyword(s):  
Nuclear Import ◽  
Nuclear Pore ◽  
Histone Chaperones ◽  
Oligomeric State ◽  
Post Translational Modifications ◽  
The Core ◽  
Transport Receptors ◽  
Import Receptors ◽  
Linear Motifs ◽  
Import Receptor

The transport of histones from the cytoplasm to the nucleus of the cell, through the nuclear membrane, is a cellular process that regulates the supply of new histones in the nucleus and is key for DNA replication and transcription. Nuclear import of histones is mediated by proteins of the karyopherin family of nuclear transport receptors. Karyopherins recognize their cargos through linear motifs known as nuclear localization/export sequences or through folded domains in the cargos. Karyopherins interact with nucleoporins, proteins that form the nuclear pore complex, to promote the translocation of their cargos into the nucleus. When binding to histones, karyopherins not only function as nuclear import receptors but also as chaperones, protecting histones from non-specific interactions in the cytoplasm, in the nuclear pore and possibly in the nucleus. Studies have also suggested that karyopherins might participate in histones deposition into nucleosomes. In this review we describe structural and biochemical studies from the last two decades on how karyopherins recognize and transport the core histone proteins H3, H4, H2A and H2B and the linker histone H1 from the cytoplasm to the nucleus, which karyopherin is the major nuclear import receptor for each of these histones, the oligomeric state of histones during nuclear import and the roles of post-translational modifications, histone-chaperones and RanGTP in regulating these nuclear import pathways.

scholarly journals Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 98 ◽  
Author(s):  
Paola Infante ◽  
Ludovica Lospinoso Severini ◽  
Flavia Bernardi ◽  
Francesca Bufalieri ◽  
Lucia Di Marcotullio
Keyword(s):  
E3 Ligase ◽  
Multiple Roles ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Promising Target ◽  
Important Pathway ◽  
Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

scholarly journals Targeting the Nuclear Import Receptor Kpnβ1 as an Anticancer Therapeutic

2016 ◽  
Vol 15 (4) ◽  
pp. 560-573 ◽  
Author(s):  
Pauline J. van der Watt ◽  
Alicia Chi ◽  
Tamara Stelma ◽  
Catherine Stowell ◽  
Erin Strydom ◽  
...  
Keyword(s):  
Nuclear Import ◽  
Import Receptor

scholarly journals Transportin Is a Major Nuclear Import Receptor for c-Fos

2006 ◽  
Vol 281 (9) ◽  
pp. 5492-5499 ◽  
Author(s):  
Marc Arnold ◽  
Annegret Nath ◽  
Daniel Wohlwend ◽  
Ralph H. Kehlenbach
Keyword(s):  
Nuclear Import ◽  
Import Receptor

scholarly journals The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

2002 ◽  
Vol 277 (36) ◽  
pp. 32480-32489 ◽  
Author(s):  
Marc Bäuerle ◽  
Detlef Doenecke ◽  
Werner Albig
Keyword(s):  
Nuclear Import ◽  
Import Receptor

scholarly journals Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites

Cell ◽  
2018 ◽  
Vol 173 (3) ◽  
pp. 693-705.e22 ◽  
Author(s):  
Takuya Yoshizawa ◽  
Rustam Ali ◽  
Jenny Jiou ◽  
Ho Yee Joyce Fung ◽  
Kathleen A. Burke ◽  
...  
Keyword(s):  
Phase Separation ◽  
Nuclear Import ◽  
Import Receptor

scholarly journals Evolutionary meandering of intermolecular interactions along the drift barrier

2014 ◽  
Vol 112 (1) ◽  
pp. E30-E38 ◽  
Author(s):  
Michael Lynch ◽  
Kyle Hagner
Keyword(s):  
Intermolecular Interactions ◽  
Binding Sites ◽  
Rna Binding ◽  
Fine Tuning ◽  
Evolutionary Divergence ◽  
Sequence Motif ◽  
Cellular Functions ◽  
Mutation Pressure ◽  
Rna Molecules ◽  
The Face

Many cellular functions depend on highly specific intermolecular interactions, for example transcription factors and their DNA binding sites, microRNAs and their RNA binding sites, the interfaces between heterodimeric protein molecules, the stems in RNA molecules, and kinases and their response regulators in signal-transduction systems. Despite the need for complementarity between interacting partners, such pairwise systems seem to be capable of high levels of evolutionary divergence, even when subject to strong selection. Such behavior is a consequence of the diminishing advantages of increasing binding affinity between partners, the multiplicity of evolutionary pathways between selectively equivalent alternatives, and the stochastic nature of evolutionary processes. Because mutation pressure toward reduced affinity conflicts with selective pressure for greater interaction, situations can arise in which the expected distribution of the degree of matching between interacting partners is bimodal, even in the face of constant selection. Although biomolecules with larger numbers of interacting partners are subject to increased levels of evolutionary conservation, their more numerous partners need not converge on a single sequence motif or be increasingly constrained in more complex systems. These results suggest that most phylogenetic differences in the sequences of binding interfaces are not the result of adaptive fine tuning but a simple consequence of random genetic drift.

scholarly journals Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Federica Di Sano ◽  
Mauro Piacentini
Keyword(s):  
Cell Death ◽  
Membrane Proteins ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Neurodegenerative Disorders ◽  
Cellular Functions ◽  
Promising Target ◽  
Specific Proteins ◽  
Structure And Functions

Reticulons (RTNs) are a group of membrane proteins localized on the ER and known to regulate ER structure and functions. Several studies have suggested that RTNs are involved in different important cellular functions such as changes in calcium homeostasis, ER-stress-mediated cell death, and autophagy. RTNs have been demonstrated to exert a cancer specific proapoptotic function via the interaction or the modulation of specific proteins. Reticulons have also been implicated in different signaling pathways which are at the basis of the pathogenesis of several neurodegenerative diseases. In this paper we discuss the accumulating evidence identifying RTN-1C protein as a promising target in the treatment of different pathologies such as cancer or neurodegenerative disorders.

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