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PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis

Authors
 Min-Sik Lee  ;  Man-Hyung Jeong  ;  Hyun-Woo Lee  ;  Hyun-Ji Han  ;  Aram Ko  ;  Stephen M. Hewitt  ;  Jae-Hoon Kim  ;  Kyung-Hee Chun  ;  Joon-Yong Chung  ;  Cheolju Lee  ;  Hanbyoul Cho  ;  Jaewhan Song 
Citation
 Nature Communications, Vol.6 : 7769-7769, 2015 
Journal Title
 Nature Communications 
ISSN
 2041-1723 
Issue Date
2015
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
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140930
DOI
10.1038/ncomms8769
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
Yonsei Authors
김재훈(Kim, Jae Hoon) ; 전경희(Chun, Kyung Hee) ; 조한별(Cho, Han Byoul)
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