title: Oncogenic function of p34SEI-1 via NEDD4‑1‑mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway.
abstract: 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.
authors: Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors: Samil
authors: S
authors: Jung
authors: Chengping
authors: C
authors: Li
authors: Dongjun
authors: D
authors: Jeong
authors: Soonduck
authors: S
authors: Lee
authors: Jiyeon
authors: J
authors: Ohk
authors: Meeyoung
authors: M
authors: Park
authors: Songyi
authors: S
authors: Han
authors: Jingjing
authors: J
authors: Duan
authors: Changjin
authors: C
authors: Kim
authors: Young
authors: Y
authors: Yang
authors: Keun-Il
authors: KI
authors: Kim
authors: Jong-Seok
authors: JS
authors: Lim
authors: Young-Sook
authors: YS
authors: Kang
authors: Myeong-Sok
authors: MS
authors: Lee
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D000075702:Nedd4 Ubiquitin Protein Ligases; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C402464:SERTAD1 protein, human; C000618483:Nedd4 protein, human; C494929:PTEN protein, human