Oncogenic function of p34(SEI-1) via NEDD4-1-mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway

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초록

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.

키워드

34-KD protein encoding selected with Ink4a-1 as bait gene; phosphatase and tensin homolog deleted on chromosome ten; neuronal precursor cell-expressed developmentally downregulated 4-1; phosphoinositide-3 kinase/protein kinase B; tumorigenesis; UBIQUITIN LIGASE NEDD4-1; INTEGRIN-LINKED KINASE; PI3K-AKT-MTOR PATHWAY; TUMOR-SUPPRESSOR; PROSTATE-CANCER; CELL-SURVIVAL; APOPTOSIS; INSTABILITY; PROGRESSION; METASTASIS
제목
Oncogenic function of p34(SEI-1) via NEDD4-1-mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway
저자
Jung, Samil; Li, Chengping; Jeong, Dongjun; Lee, Soonduck; Ohk, Jiyeon; Park, Meeyoung; Han, Songyi; Duan, Jingjing; Kim, Changjin; Yang, Young; Kim, Keun-Il; Lim, Jong-Seok; Kang, Young-Sook; Lee, Myeong-Sok
DOI
10.3892/ijo.2013.2064
발행일
2013-11
유형
Article
저널명
International Journal of Oncology
권
43
호
5
페이지
1587 ~ 1595