Molecular Simulations of Polycation–DNA Binding Exploring the Effect of Peptide Chemistry and Sequence in Nuclear Localization Sequence Based Polycations

2013 ◽  
Vol 117 (40) ◽  
pp. 11988-11999 ◽  
Author(s):  
Robert M. Elder ◽  
Arthi Jayaraman
Keyword(s):  
Dna Binding ◽  
Nuclear Localization ◽  
Molecular Simulations ◽  
Nuclear Localization Sequence ◽  
Peptide Chemistry ◽  
Localization Sequence

scholarly journals Specificity of Rel-inhibitor interactions in Drosophila embryos.

1995 ◽  
Vol 15 (7) ◽  
pp. 3627-3634 ◽  
Author(s):  
K Tatei ◽  
M Levine
Keyword(s):  
Dna Binding ◽  
Nuclear Localization ◽  
Function Analysis ◽  
Nuclear Localization Sequence ◽  
Sequence Motif ◽  
Composite Surface ◽  
Region I ◽  
Localization Sequence ◽  
Drosophila Embryos

The Rel family of transcription factors participate in a diverse array of processes, including acute responses to injury and infection, lymphocyte differentiation, and embryonic patterning. These proteins show homology in an extended region spanning about 300 amino acids (the Rel homology domain [RHD]). The RHD mediates both DNA binding and interactions with a family of inhibitor proteins, including I kappa B alpha and cactus. Previous studies have shown that an N-terminal region of the RHD (containing the sequence motif RXXRXRXXC) is important for DNA binding, while the C-terminal nuclear localization sequence is important for inhibitor interactions. Here we present a structure-function analysis of the Drosophila dorsal RHD. These studies identify another sequence within the RHD (region I) that is essential for inhibitor interactions. There is a tight correlation between the conservation of region I sequences and the specificity of Rel-inhibitor interactions in both flies and mammals. Point mutations in the region I sequence can uncouple DNA binding and inhibitor interactions in vitro. The phenotypes associated with the expression of a modified dorsal protein in transgenic Drosophila embryos suggest a similar uncoupling in vivo. Recent crystallographic studies suggest that the region I sequence and the nuclear localization sequence might form a composite surface which interacts with inhibitor proteins.

scholarly journals G Protein-Coupled Receptor Kinase 5 Contains a DNA-Binding Nuclear Localization Sequence

2004 ◽  
Vol 24 (23) ◽  
pp. 10169-10179 ◽  
Author(s):  
Laura R. Johnson ◽  
Mark G. H. Scott ◽  
Julie A. Pitcher
Keyword(s):  
Dna Binding ◽  
G Protein ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Calcium Ionophore ◽  
Nuclear Localization Sequence ◽  
G Protein Coupled Receptor ◽  
Gpcr Activation ◽  
Localization Sequence ◽  
G Protein Coupled

ABSTRACT G protein-coupled receptor kinases (GRKs) mediate desensitization of agonist-occupied G protein-coupled receptors (GPCRs). Here we report that GRK5 contains a DNA-binding nuclear localization sequence (NLS) and that its nuclear localization is regulated by GPCR activation, results that suggest potential nuclear functions for GRK5. As assessed by fluorescence confocal microscopy, transfected and endogenous GRK5 is present in the nuclei of HEp2 cells. Mutation of basic residues in the catalytic domain of GRK5 (between amino acids 388 and 395) results in the nuclear exclusion of the mutant enzyme (GRK5Δ NLS), demonstrating that GRK5 contains a functional NLS. The nuclear localization of GRK5 is subject to dynamic regulation. Calcium ionophore treatment or activation of Gq-coupled muscarinic-M3 receptors promotes the nuclear export of the kinase in a Ca2+/calmodulin (Ca2+/CaM)-dependent fashion. Ca2+/CaM binding to the N-terminal CaM binding site of GRK5 mediates this effect. Furthermore, GRK5, but not GRK5Δ NLS or GRK2, binds specifically and directly to DNA in vitro. Consistent with their presence in the nuclei of transfected cells, all the GRK4, but not GRK2, subfamily members contain putative NLSs. These results suggest that the GRK4 subfamily of GRKs may play a signaling role in the nucleus and that GRK4 and GRK2 subfamily members perform divergent cellular functions.

scholarly journals Loss of IκBα-Mediated Control over Nuclear Import and DNA Binding Enables Oncogenic Activation of c-Rel

1998 ◽  
Vol 18 (9) ◽  
pp. 5445-5456 ◽  
Author(s):  
Shrikesh Sachdev ◽  
Mark Hannink
Keyword(s):  
Dna Binding ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Nuclear Export ◽  
Specific Inhibitor ◽  
Nuclear Localization Sequence ◽  
Treatment Results ◽  
Leptomycin B ◽  
Localization Sequence ◽  
Nuclear Shuttling

ABSTRACT The IκBα protein is able both to inhibit nuclear import of Rel/NF-κB proteins and to mediate the export of Rel/NF-κB proteins from the nucleus. We now demonstrate that the c-Rel–IκBα complex is stably retained in the cytoplasm in the presence of leptomycin B, a specific inhibitor of Crm1-mediated nuclear export. In contrast, leptomycin B treatment results in the rapid and complete relocalization of the v-Rel–IκBα complex from the cytoplasm to the nucleus. IκBα also mediates the rapid nuclear shuttling of v-Rel in an interspecies heterokaryon assay. Thus, continuous nuclear export is required for cytoplasmic retention of the v-Rel–IκBα complex. Furthermore, although IκBα is able to mask the c-Rel-derived nuclear localization sequence (NLS), IκBα is unable to mask the v-Rel-derived NLS in the context of the v-Rel–IκBα complex. Taken together, our results demonstrate that IκBα is unable to inhibit nuclear import of v-Rel. We have identified two amino acid differences between c-Rel and v-Rel (Y286S and L302P) which link the failure of IκBα to inhibit nuclear import and DNA binding of a mutant c-Rel protein to oncogenesis. Our results support a model in which loss of IκBα-mediated control over c-Rel leads to oncogenic activation of c-Rel.

scholarly journals Identification of a nuclear localization sequence within the structure of the human interleukin-1 alpha precursor.

1993 ◽  
Vol 268 (29) ◽  
pp. 22100-22104
Author(s):  
J.H. Wessendorf ◽  
S Garfinkel ◽  
X Zhan ◽  
S Brown ◽  
T Maciag
Keyword(s):  
Nuclear Localization ◽  
Interleukin 1 ◽  
Nuclear Localization Sequence ◽  
Localization Sequence

Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification

2003 ◽  
Vol 49 (5) ◽  
pp. 1297-1307 ◽  
Author(s):  
Lars Fichtner ◽  
Daniel Jablonowski ◽  
Angelika Schierhorn ◽  
Hiroko K. Kitamoto ◽  
Michael J. R. Stark ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Sequence ◽  
Post Translational Modification ◽  
Sequence Dependent ◽  
Localization Sequence
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