PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis
- PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis
- 이민식; 정만형; 이현우; 한현지; 고아람; Hewitt SM; 김재훈; 전경희; 정준영; 이철주; 조한별; 송재환
- Issue Date
- Nature Communications
- VOL 6, 7769
- The activity of the phosphatase and tensin homologue (PTEN) is known to be suppressed via post-translational modification. However, the mechanism and physiological significance by which post-translational modifications lead to PTEN suppression remain unclear. Here we demonstrate that PTEN destabilization is induced by EGFR-or oncogenic PI3K mutation-mediated AKT activation in cervical cancer. EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 ligase. These processes require the stabilization of MKRN1 via AKT-mediated phosphorylation. In cervical cancer patients with high levels of pAKT and MKRN1 expression, PTEN protein levels are low and correlate with a low 5-year survival rate. Taken together, our results demonstrate that PI3K/AKT signals enforce positive-feedback regulation by suppressing PTEN function.
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