Open AccessOncogenic function of p34SEI-1 via NEDD4-1-mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway
Author(s) -
Samil Jung,
Chengping Li,
Dongjun Jeong,
Soonduck Lee,
Jiyeon Ohk,
Meeyoung Park,
Shuang Han,
Jingjing Duan,
Changjin Kim,
Young Yang,
Keun-Il Kim,
JongSeok Lim,
YoungSook Kang,
MyeongSok Lee
Publication year - 2013
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2013.2064
Subject(s) - pten , ubiquitin , biology , nedd4 , pi3k/akt/mtor pathway , oncogene , protein kinase b , cancer research , function (biology) , microbiology and biotechnology , cell cycle , cancer , ubiquitin ligase , signal transduction , genetics , gene
A 34-KD protein encoded by the SEI-1 gene (p34(SEI‑1)), is a relatively recently discovered oncoprotein that has multiple important biological functions. Our data show that p34(SEI-1) enhances cancer cell survival and promotes tumorigenesis by downregulating the tumor suppressor PTEN, a negative regulator of the PI3K/AKT signaling pathway, and therefore activating the PI3K/AKT signaling pathway. In this process, p34(SEI-1) positively affects NEDD4-1 gene expression both at the transcriptional and protein levels. Furthermore, the expression levels of p34(SEI-1) and NEDD4-1 were found to be coordinated in tumor tissues obtained from patients with breast cancer. We also show that p34(SEI-1) affects the subcellular localization of PTEN.