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

Inoue, H.; Ndong, Moussa; Suzuki, Takahiro; Kazami, Machiko; Uyama, Takumi; Kobayashi, Kenichi; Tadokoro, Tadahiro; Yamamoto, Yuji

doi:10.1271/bbb.90489

Cited by 8 publications

(4 citation statements)

References 27 publications

(24 reference statements)

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“…HSP70 (heat shock protein 70) has been shown to interact with RICTOR for the formation and activity of mTORC2 in addition to the interaction with TSC1 and TSC2 (Martin et al, 2008;Inoue et al, 2009) (Figure 3C). HSP70-1/HSP70-3 double knockout mice are more susceptible to ischemiainduced damages (Kim et al, 2006).…”

Section: Hsp70mentioning

confidence: 99%

Frontier of Epilepsy Research - mTOR signaling pathway

Cho

2011

Exp Mol Med

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Section: Hsp70mentioning

confidence: 99%

Frontier of Epilepsy Research - mTOR signaling pathway

Cho

2011

Exp Mol Med

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“…In 2009, Inoue et al have given the first proof that HSP70 interacts with TSC1 using far-western blot and mass spectrometry. 15 Nevertheless, the mechanism or the region of interaction was not commented on. In general, DnaK binds to the substrates that have a stretch of hydrophobic residues flanked by positively charged amino acids.…”

Section: Discussionmentioning

confidence: 99%

“…In this case, TSC1 can be a substrate or a co-chaperone to HSP70. In 2009, Inoue et al have given the first proof that HSP70 interacts with TSC1 using far-western blot and mass spectrometry . Nevertheless, the mechanism or the region of interaction was not commented on.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, phosphorylation of TSC2 by LKB1-AMPK plays an important role in the cell stress pathway (hypoxia, DNA damage, and low energy). − Inoue et al have shown TSC1 interaction with HSP70 proven with far-western blot and mass spectrometry in the mammalian expression system . Also, the importance of T417 of TSC1 for interaction with HSP70 and co-localization of this protein complex on the mitochondrial membrane preventing apoptosis has also been shown in another study …”

Section: Introductionmentioning

confidence: 89%

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Recombinant Tumor Suppressor TSC1 Differentially Interacts with Escherichia coli DnaK and Human HSP70

2020

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Tuberous sclerosis complex (TSC) is a neurological syndrome manifested by non-cancerous tumors in several organs. Mutations in either TSC1 or TSC2 tumor suppressor gene cause the disease. In the cell, TSC1 is known to form a heterodimer with TSC2 because of which an active complex is formed that negatively regulates the mTORC1 activity during cellular stress. Hence, mutation in TSC1 or TSC2 is manifested by excess proliferation of the cells leading to the development of numerous benign tumors. The TSC1 and TSC2 complex is known to interact with several protein-binding partners. One such significant interaction of this complex is with the molecular chaperone HSP70. The role of TSC1 in that interaction is still elusive. Here, we have expressed and purified TSC1 (302–420 residues) in a bacterial expression system and have shown that this region directly interacts with HSP70. We have shown that TSC1 increases the ATPase activity of Escherichia coli DnaK, a HSP70 homologue. On the contrary, TSC1 was found to show inhibitory activity toward human HSP70. Our result suggests that TSC1 (302–420 aa) shows differential interaction between the HSP70 homologues. This points toward the evolutionary significance of chaperoning system and the importance of eukaryotic tetratricopeptide repeat domain interaction motif -EEVD. Our study shows the evidence that TSC1 interacts with HSP70 and has a role to play in the chaperoning activity to maintain cellular homeostasis.

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