The TSC1 gene product hamartin interacts with NADE

Brain-Expressed X-linked (BEX) proteins in human cancers

“…Activation of caspase-2 and caspase-3 was observed in BEX3 expressing cells in response to NGF suggesting that BEX3 mediated apoptosis 6 is mediated through activation of caspases [28]. In addition, BEX3 binds to hamartin, a protein expressed by the tuberous sclerosis complex 1 (TSC1) gene [63]. Sporadic mutations in TSC1 is associated with a rare multi-system genetic disease tuberous sclerosis causing benign tumors in the brain or other organs [64].…”

“…Sporadic mutations in TSC1 is associated with a rare multi-system genetic disease tuberous sclerosis causing benign tumors in the brain or other organs [64]. Association of hamartin, and BEX3 were required for NGF-induced apoptosis in PC12h cells, as siRNA-mediated knockdown of TSC1 gene in BEX3 overexpressing cells were protected from NGF-induced apoptosis [63]. Another class of NGF receptor TrkA was associated with BEX3 through the juxtamembrane domain of the receptor.…”

Hamartin-Hsp70 Interaction Is Necessary for Akt-Dependent Tuberin Phosphorylation during Heat Shock

“…[9][10][11] This study indicates that the Akt-tuberin signal is activated during heat shock stress by binding of hamartin to Hsp70.…”

“…In previous studies, stress-related proteins, e.g., NADE, 11) bound hamartin, suggesting that hamartin participates in the stress response. Moreover, Hsp70-1 and Hsc70 were recently identified as novel tuberinbinding proteins in HEK293 cells, 19) but the mechanisms by which tuberin and Hsp70 bind together and the nature of the hamartin interaction with this complex remain unclear.…”

“…6,7) Akt and other factors phosphorylate tuberin and inhibit its downstream signaling targets, including Rheb, the mammalian target of rapamycin (mTOR), and the ribosomal protein S6 kinase (S6K), via the hamartintuberin complex. 8) Phosphorylation of hamartin and/or tuberin might play an important role in the formation of the hamartin-tuberin complex under various stress conditions, including hypoxia, low energy, and DNA damage, [9][10][11] but the regulatory mechanisms underlying the association of hamartin and tuberin under stress have not been well documented.…”