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Cross‐talk between tuberin, calmodulin, and estrogen signaling pathways
Author(s) -
York Brian,
Lou Dingyuan,
Panettieri Reynold A.,
Krymskaya Vera P.,
Vanaman Thomas C.,
Noonan Daniel J.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3142fje
Subject(s) - estrogen receptor , tuberous sclerosis , biology , estrogen , microbiology and biotechnology , estrogen receptor alpha , calmodulin , intracellular , lymphangioleiomyomatosis , biochemistry , endocrinology , genetics , medicine , cancer , psychiatry , breast cancer , enzyme
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 α (ERα). In the study presented here, tuberin was shown to co‐immunoprecipitate and directly bind ERα 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 ERα and CaM. Additionally, tuberin‐ERα 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 ERα‐mediated gene transcription events. Cumulatively, data presented here support the hypothesis that interactions between tuberin, ERα, and CaM may play a critical role in the pathology of LAM disease.