Hamartin-Hsp70 interaction is necessary for Akt-dependent tuberin phosphorylation during heat shock.
Hamartin and tuberin interact directly to regulate cell growth negatively. In this study, far-western blotting revealed that hamartin binds directly Heat shock protein 70 (Hsp70), even in the absence of tuberin. While the hamartin-tuberin complex acts as a sensor for a variety of types of stress, it is unclear how the complex is regulated under stress conditions. We found that the hamartin-Hsp70 interaction is stabilized during heat shock. On the other hand, tuberin underwent degradation through phosphorylation in an Akt-dependent manner. Furthermore, we found that when Hsp70 expression was inhibited by N-formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolactam (KNK437), Akt phosphorylation on site Ser308 diminished and tuberin was not phosphorylated at Thr1462 during heat shock. We conclude that both hamartin and Hsp70 increase in response to heat shock, whereas tuberin is phosphorylated and thereafter degraded via the PI3K/Akt pathway. Through this pathway, hamartin-Hsp70 plays a crucial role as a scaffolding protein that transfers the Akt signal to tuberin.
Inoue
Hirohumi
H
Department of Applied Biology and Chemistry, Tokyo University of Agriculture, Tokyo, Japan.
Ndong
Moussa
M
Suzuki
Tsukasa
T
Kazami
Machiko
M
Uyama
Takumi
T
Kobayashi
Ken-Ichi
K
Tadokoro
Tadahiro
T
Yamamoto
Yuji
Y
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013057:Spectrum Analysis; D013912:Threonine; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D013912:Threonine; D051057:Proto-Oncogene Proteins c-akt