Sep 23, 2020 · Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4 and accelerates the ubiquitin-mediated degradation of FOXO4.

Here we show that EGF, PKB/Akt, CSN6, and COP1 have oncogenic activities in regulating FOXO4. COP1 is identified here as an E3 ubiquitin ligase that binds and destabilizes FOXO4. Notably, FOXO4 inhibits SGOC pathway metabolic reprogramming of cancer.

The COP1 coat protein complex mediates retrograde transport through the Golgi and to the ER, and depletion of COP1 was also recently shown to inhibit EGF-stimulated transport of EGFR to the nucleus .

In this study, we characterize the upstream regulators of the FOXO4 in tumorigenesis including EGF, PKB/Akt, CSN6 and COP1. In addition, new FOXO4 downstream targets involved in serine-glycine-one-carbon (SGOC) amino acid metabolism are characterized.

Sep 23, 2020 · Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4...

Sep 23, 2020 · Here we show that EGF, PKB/Akt, CSN6, and COP1 have oncogenic activities in regulating FOXO4. COP1 is identified here as an E3 ubiquitin ligase that binds and destabilizes FOXO4. Notably, FOXO4 inhibits SGOC pathway metabolic reprogramming of cancer.

Our studies provide important insight into the signaling role of the EGF‐PKB/Akt‐CSN6‐COP1 axis in enhancing ubiquitin‐mediated FOXO4 degradation during tumorigenesis and elucidate a …

Oct 29, 2021 · We show that the tumor suppressor E3 ligase COP1 promotes the degradative polyubiquitination of the microtubule-associated protein HPIP. As such, COP1 negatively regulates estrogen-dependent...

Sep 23, 2020 · Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4 and accelerates the ubiquitin‐mediated degradation of FOXO4.

Here, it is reported that FOXO4 levels are downregulated in response to EGF treatment, with concurrent elevation of COP9 Signalosome subunit 6 (CSN6) and E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) levels.