A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 176

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Signals and pathways regulating nucleolar retention of novel putative nucleolar GTPase NGP-1(GNL-2). | LitMetric

NGP-1(GNL-2) is a putative GTPase, overexpressed in breast carcinoma and localized in the nucleolus. NGP-1 belongs to the MMR1-HSR1 family of large GTPases that are emerging as crucial coordinators of signaling cascades in different cellular compartments. The members of this family share very closely related G-domains, but the signals and pathways regulating their subcellular localization and their functional relevance remain unknown. To improve our understanding of the nuclear transport mechanism of NGP-1, we have identified two nucleolar localization signals (NoLS) that are independently shown to translocate NGP-1 as well the heterologous protein to the nucleolus. Site-specific mutagenesis and immunofluorescence studies suggest that the tandem repeats of positively charged amino acids are critical for NGP-1 NoLS function. Interestingly, amino-terminal (NGP-1(1-100)) and carboxyl-terminal (NGP-1(661-731)) signals independently interact with receptors importin-β and importin-α, respectively. This investigation, for the first time, provides evidence that the interaction of importin-α with C-terminal NoLS (NGP-1(661-731)) was able to target the heterologous protein to the nucleolar compartment. Structural modeling analysis and alanine scanning mutagenesis of conserved G-domains suggest that G4 and G5 motifs are critical for GTP binding of NGP-1 and further show that the nucleolar localization of NGP-1 is regulated by a GTP gating-mediated mechanism. In addition, our data suggest that an ongoing transcription is essential for efficient localization of NGP-1 to the nucleolus. We have observed a high level of NGP-1 expression in the mitogen-activated primary human peripheral blood mononuclear cells (hPBMC) as well as in human fetal brain-derived neural precursor cells (hNPCs) in comparison to cells undergoing differentiation. Overall, the results suggest that multiple mechanisms are involved in the localization of NGP-1 to the nucleolus for the regulation of nucleolar function in cell growth and proliferation.

Download full-text PDF

Source
http://dx.doi.org/10.1021/bi200425bDOI Listing

Publication Analysis

Top Keywords

localization ngp-1
12
ngp-1
9
signals pathways
8
pathways regulating
8
nucleolar localization
8
heterologous protein
8
ngp-1 nucleolus
8
nucleolar
6
localization
5
signals
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!