Identification and Characterization of the Interaction between Tuberin and 14-3-3ζ
Open Access
- 1 October 2002
- journal article
- Published by Elsevier BV
- Vol. 277 (42), 39417-39424
- https://doi.org/10.1074/jbc.m204802200
Abstract
Tuberous sclerosis is caused by mutations to either the TSC1 or TSC2 tumor suppressor gene. The disease is characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction, and dermatological abnormalities. TSC1 encodes a 130-kDa protein called hamartin, and TSC2 encodes a 200-kDa protein called tuberin. Although it has been shown that hamartin and tuberin form a complex and mediate phosphoinositide 3-kinase/Akt-dependent phosphorylation of the ribosomal protein S6, it is not yet clear how inactivation of either protein leads to tuberous sclerosis. Therefore, to obtain additional insight into tuberin and hamartin function, yeast two-hybrid screening experiments were performed to identify proteins that interact with tuberin. One of the proteins identified was 14-3-3ζ, a member of the 14-3-3 protein family. The interaction between tuberin and 14-3-3ζ was confirmed in vitro and by co-immunoprecipitation; multiple sites within tuberin for 14-3-3ζ binding were identified; and it was determined that 14-3-3ζ associated with the tuberin-hamartin complex. Finally, it was shown that the tuberin/14-3-3ζ interaction is regulated by Akt-mediated phosphorylation of tuberin, providing insight into how tuberin may regulate phosphorylation of S6.Keywords
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