title: p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN.
abstract: PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.
authors.affiliation: 1] Innovative Cancer Research, Asan Medical Center, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul, Republic of Korea [2] Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: S-W
authors.initials: SW
authors.lastname: Hong
authors.forename: J-H
authors.initials: JH
authors.lastname: Moon
authors.forename: J-S
authors.initials: JS
authors.lastname: Kim
authors.forename: J-S
authors.initials: JS
authors.lastname: Shin
authors.forename: K-A
authors.initials: KA
authors.lastname: Jung
authors.forename: W-K
authors.initials: WK
authors.lastname: Lee
authors.forename: S-Y
authors.initials: SY
authors.lastname: Jeong
authors.forename: J J
authors.initials: JJ
authors.lastname: Hwang
authors.forename: S-J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Y-A
authors.initials: YA
authors.lastname: Suh
authors.forename: I
authors.initials: I
authors.lastname: Kim
authors.forename: K-Y
authors.initials: KY
authors.lastname: Nam
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.forename: J E
authors.initials: JE
authors.lastname: Kim
authors.forename: K-P
authors.initials: KP
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Hong
authors.forename: J-L
authors.initials: JL
authors.lastname: Lee
authors.forename: W-J
authors.initials: WJ
authors.lastname: Lee
authors.forename: E K
authors.initials: EK
authors.lastname: Choi
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: D-H
authors.initials: DH
authors.lastname: Jin
authors.forename: T W
authors.initials: TW
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D000075702:Nedd4 Ubiquitin Protein Ligases; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase