HSP70 interacts with Rheb, inhibiting mTORC1 signaling.

Abstract:

: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.

authors

Ryu HH,Ha SH

doi

10.1016/j.bbrc.2020.07.053

subject

Has Abstract

pub_date

2020-12-17 00:00:00

pages

1198-1203

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)31442-X

journal_volume

533

pub_type

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