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: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
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
The alveolar rhabdomyosarcoma-associated t(2;13) chromosomal translocation produces an oncogenic fusion transcription factor PAX3-FKHR that combines the N-terminal DNA binding domains (paired domain and homeodomain) of PAX3 with the C-terminal activation domain of FKHR. In the context of PAX3-FKHR, the two DNA binding domains can work either cooperatively or autonomously in regulating gene transcription. The latter is a gain-of-function unique to the fusion protein. The biological activities driven by the individual DNA binding domain remains poorly defined. In this study, we express PAX3-FKHR mutants that contain only a single functional DNA binding domain into C2C12 myoblasts, and measured the in vitro and in vivo behaviors of these cells. We show that only the homeodomain-specific PAX3-FKHR mutant recapitulates the in vitro transformation properties of the wild type fusion protein. However, despite the differential responses in vitro, both the paired domain- and the homeodomain-specific PAX3-FKHR mutants promote tumor development from myoblasts in vivo. Our results suggest an important role for the gain of the paired domain- and the homeodomain-transcription activities in the PAX3-FKHR malignant transformation process.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615594 | PMC |
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