PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis

Title
PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis
Authors
이민식정만형이현우한현지고아람Hewitt SM김재훈전경희정준영이철주조한별송재환
Issue Date
2015-07
Publisher
Nature Communications
Citation
VOL 6, 7769
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/50540
ISSN
20411723
Appears in Collections:
KIST Publication > Article
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