Document Detail

Interactions between BdkrB2 and p53 genes in the developing kidney.
MedLine Citation:
PMID:  23152407     Owner:  NLM     Status:  Publisher    
Abstract Gene-environment interactions are implicated in congenital disorders. Accordingly, there is a pressing need to develop animal models of human disease, which are the product of defined gene-environment interactions. Work from our laboratory demonstrates the presence of genetic interactions between the bradykinin B2 receptor (Bdkrb2) and the tumor suppressor protein p53 in the developing kidney. Our studies have shown that Bdkrb2-/- embryos exposed to gestational salt stress develop renal dysgenesis. The underlying mechanism is p53 stabilization and -mediated apoptosis and repression of the terminal epithelial differentiation program. We also uncovered a novel functional cross-talk between p53 and BdkrB2. Thus, while BdkrB2 is a target for p53-mediated transcriptional activation, BdkrB2 inactivation results in upregulation of Checkpoint Kinase 1 (Chk1) levels, thus potentiating phosphorylation of p53 on Ser23 by Chk1, an essential step in the pathway leading to renal dysgenesis in salt-stressed BdkrB2-/- mutant mice. Future studies will now focus on defining how this G-protein coupled receptor is coupled to activation of p53, a tumor suppressor gene that is mutated in more than 50% of all human cancers.
Samir S El-Dahr; Zubaida Saifudeen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Biological chemistry     Volume:  -     ISSN:  1437-4315     ISO Abbreviation:  Biol. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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