Cross-talk between tuberin, calmodulin, and estrogen signaling pathways.
Lymphangioleiomyomatosis (LAM) is a rare disease that occurs primarily in women and has been linked to both estrogen-mediated signaling events and mutations associated with the tuberous sclerosis complex 2 gene product tuberin. These two observations fostered the hypothesis that tuberin's impact on estrogen-mediated signaling might be through a direct interaction ... with the intracellular receptor for estrogen, estrogen receptor alpha (ERalpha). In the study presented here, tuberin was shown to co-immunoprecipitate and directly bind ERalpha through a domain localized within the carboxyl 73 amino acids of tuberin. This domain had previously been shown to serve as a binding domain for the intracellular calcium signaling molecule calmodulin (CaM). Competition binding studies identified a potential competitive relationship for binding of tuberin by ERalpha and CaM. Additionally, tuberin-ERalpha interactions were found to be modulated by the presence of tuberin's predominant intracellular binding partner hamartin, suggesting that tuberin-hamartin interactions negatively impact the ability of tuberin to modulate ERalpha-mediated gene transcription events. Cumulatively, data presented here support the hypothesis that interactions between tuberin, ERalpha, and CaM may play a critical role in the pathology of LAM disease.
Mesh Terms:
Binding, Competitive, Calmodulin, DNA, Estrogen Receptor alpha, Estrogens, Female, Humans, Lymphangioleiomyomatosis, Signal Transduction, Transcription, Genetic, Tumor Suppressor Proteins
Binding, Competitive, Calmodulin, DNA, Estrogen Receptor alpha, Estrogens, Female, Humans, Lymphangioleiomyomatosis, Signal Transduction, Transcription, Genetic, Tumor Suppressor Proteins
FASEB J.
Date: Jul. 01, 2005
PubMed ID: 15851513
View in: Pubmed Google Scholar
Download Curated Data For This Publication
153592
Switch View:
- Interactions 7