2014年7月29日 · In various breast cancer cell lines, we found that SIRT6 was phosphorylated at Ser(338) by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation.

2021年3月16日 · Sirt6 controls the activity of MDM2, stimulating ROS production. Sirt6 also influences MDM2 to suppress Sirt1 activity, thereby also promoting cancer cell death.

2020年9月11日 · In lipopolysaccharide-induced FLSs, miR-23a inhibited the expression of MDM2, and overexpression of MDM2 partially rescued the inhibitory effect of miR-23a on FLS proliferation and inflammatory response. Mechanistically, MDM2 ubiquitination degraded SIRT6 in …

2014年8月5日 · MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer. Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor. Identification of molecular regulators of SIRT6 might enable its activation therapeutically in cancer patients.

Here, we show that AKT1 phosphorylates SIRT6 at Ser 338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser 338 phosphorylation prevents its degradation by MDM2 and results in inhibition of cell proliferation and breast cancer tumorigenesis in vivo.

Sirt6 induced cell death, as widely reported, but Sirt1 contributed to cell death only when it was suppressed by Sirt6 via regulation of MDM2. Sirt6 and Sirt6-mediated suppression of Sirt1...

2014年12月1日 · Here, we show that AKT1 phosphorylates SIRT6 at Ser338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking...

2014年7月29日 · In various breast cancer cell lines, we found that SIRT6 was phosphorylated at Ser 338 by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation.

To target SIRT6 for proteasome-dependent degradation, the kinase AKT1 phosphorylates SIRT6 at Ser338 and induces the ubiquitination of SIRT6 by MDM2 . Overexpressing MDM2 decreases the abundance of SIRT6 in cells, while inhibiting AKT1 or preventing SIRT6 phosphorylation by mutating Ser338 prevented the degradation of SIRT6 ( 167 ).

The effects of Sirt6 and Sirt1 combine to regulate ROS-induced cancer cell death. Sirt6 controls the activity of MDM2, stimulating ROS production. Sirt6 also influences MDM2 to suppress Sirt1 activity, thereby also promoting cancer cell death. Drugs affecting these three proteins could offer new approaches to anti-cancer therapy. Introduction