2022年8月24日 · Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylatio …

2011年11月1日 · Akt inhibits FOXO through direct phosphorylation, and indirectly activates mTORC1, which in turn elevates protein synthesis. mTORC1 and its downstream effector, S6K, elicit negative feedback loops to inhibit Akt. When activated FOXO induces the expression of Sestrin 3, which activates AMPK to inhibit mTORC1.

2010年4月20日 · Activated FoxO1 inhibits mTORC1 by TSC2-dependent and TSC2-independent mechanisms. First, FoxO1 induces Sestrin3 (Sesn3) gene expression. Sesn3, in turn, inhibits mTORC1 activity in Tsc2-proficient cells. Second, FoxO1 elevates the expression of Rictor, leading to increased mTORC2 activity that consequently activates Akt.

2010年4月20日 · Activated FoxO1 inhibits mTORC1 by TSC2-dependent and TSC2-independent mechanisms. First, FoxO1 induces Sestrin3 (Sesn3) gene expression. Sesn3, in turn, inhibits mTORC1 activity in Tsc2-proficient cells. Second, FoxO1 elevates the expression of Rictor, leading to increased mTORC2 activity that consequently activates Akt.

2021年7月12日 · In addition to a role for mTORC2 as a regulator of FOXO through AKT-induced phosphorylation and cytoplasmic localization, mTORC2 has been shown to directly interact with and suppress SIRT6, whereas inactivation through RICTOR knockdown lifts SIRT6 suppression and promotes FOXO1 deacetylation and nuclear translocation (Jung et al., 2019).

2019年3月1日 · AZD8055 treatment partially reversed FOXO1 inactivation downstream of BCR crosslinking, significantly inhibiting FOXO1 T24 phosphorylation in an mTORC2-AKT-dependent manner, to promote FOXO1 nuclear localization, activity, and FOXO1-mediated gene regulation. FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib.

4 天之前 · Dual mTORC1/2 inhibition may be more effective than mTORC1 inhibition alone. mTORC2 is a central node driving enhanced ... phosphorylation of targets including the pro-apoptotic FOXO transcription ...

2013年11月5日 · We show that mTORC2 promotes inactivating phosphorylation of class IIa histone deacetylases, which leads to the acetylation of FoxO1 and FoxO3, and this in turn releases c-Myc from a suppressive miR-34c-dependent network.

2014年2月18日 · These results suggest that inactivation of mTORC1 strongly activated Akt via activation of mTORC2 and abrogation of the negative-feedback inhibition mediated by Grb10. Activated Akt phosphorylates FoxO transcription factors and suppresses their nuclear function .

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination.