HSP70 interacts with Rheb, inhibiting mTORC1 signaling
Autor: | Hyang Hwa Ryu, Sang Hoon Ha |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Biophysics mTORC1 Mechanistic Target of Rapamycin Complex 1 Biochemistry DNA-binding protein 03 medical and health sciences 0302 clinical medicine Humans Small GTPase HSP70 Heat-Shock Proteins Shotgun proteomics Molecular Biology biology Chemistry Protein Stability Binding protein Cell Biology Hsp70 Cell biology 030104 developmental biology HEK293 Cells Mtorc1 signaling 030220 oncology & carcinogenesis biology.protein Ras Homolog Enriched in Brain Protein biological phenomena cell phenomena and immunity RHEB Signal Transduction |
Zdroj: | Biochemical and biophysical research communications. 533(4) |
ISSN: | 1090-2104 |
Popis: | The small GTPase Rheb binds and activates mTORC1, which plays a pivotal role in diverse cellular physiologies. To increase our understanding of how Rheb regulates mTORC1 signaling, we set out to identify Rheb binding proteins using shotgun proteomics approaches. In this study, we characterized HSP70, one of the identified proteins, as a new Rheb binding protein. The present study showed that Rheb forms a complex with HSP70 in intact cells. Interestingly, the binding of Rheb to mTORC1 was abolished by HSP70. Furthermore, the stability of Rheb is dramatically decreased by HSP70, and this degradation is proteasome-dependent. As a result, Rheb-dependent mTORC1 activation was decreased by HSP70. Taken together, HSP70 dissociates Rheb from mTORC1 and induces proteasome-dependent degradation, leading to the inhibition of mTORC1 signaling. Our findings suggest that HSP70 is a negative regulator of mTORC1 signaling via interaction with Rheb. |
Databáze: | OpenAIRE |
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