Methionine controls insulin/mammalian target of rapamycin complex 1 activity by modulating tuberous sclerosis complex 2 stability.

Abstract:

:Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein that is partially regulated by insulin, energy, oxygen, and growth factors. Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1 (mTORC1) activation. Furthermore, S-adenosylmethionine (SAM) sensor upstream of mTORC1 indirectly inhibits mTORC1 activity via the methionine metabolite SAM. Here, we investigated the effects of methionine on insulin/TSC2/mTORC1 activity. Our results showed that methionine affected TSC2 stability and abolished TSC2 localization to the lysosome. Moreover, activation of insulin signaling contributed to TSC2 degradation in a methionine deprivation-dependent manner. Thus, methionine and insulin crosstalk occurred via TSC2.

authors

Gen S,Matsumoto Y,Suzuki T,Inoue J,Yamamoto Y

doi

10.1016/j.bbrc.2021.01.033

subject

Has Abstract

pub_date

2021-01-19 00:00:00

pages

84-89

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(21)00068-1

journal_volume

541

pub_type

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