PMID- 25809873
OWN - NLM
STAT- MEDLINE
DCOM- 20150715
LR  - 20211203
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 48
IP  - 3
DP  - 2015 Jun
TI  - Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy.
PG  - 338-47
LID - 10.1111/cpr.12184 [doi]
AB  - OBJECTIVES: Nedd4 (neural precursor cell expressed developmentally down-regulated 
      protein 4) is a member of the HECT E3 ubiquitin ligases, and is elevated in 
      prostate, bladder and colorectal cancers, and promotes colonic cell population 
      expansion. Up to now, molecular mechanisms of how Nedd4 functions, have not been 
      well understood. MATERIALS AND METHODS: In this study, shRNA was used to reduce 
      expression of Nedd4 in the human prostate carcinoma cell line DU145. To analyse 
      effects of Nedd4 on cell proliferation, MTT and colony formation assays were 
      performed. DAPI staining and FACS analysis were used to investigate outcomes of 
      Nedd4 activity, on apoptosis. Results of Nedd4 expression on lysosomal membrane 
      permeabilization and autophagy were further investigated using acridine orange 
      (AO) staining, immunofluorescence and western blot analysis. RESULTS: We found 
      that in HeLa cells, expression of Nedd4 promoted cell proliferation, whereas its 
      knockdown inhibited colony formation and induced apoptosis in DU145 cells. 
      Furthermore, down-regulation of Nedd4 in DU145 cells promoted lysosomal membrane 
      permeabilization. We also found that down-regulation of Nedd4 inhibited autophagy 
      in both DU145 and A549 cells. Investigation into mechanisms involved revealed 
      that knockdown of endogenous Nedd4 expression notably increased activated mTOR 
      (p-mTOR) levels, which suggests that mTOR signalling was involved in the 
      Nedd4-mediated autophagy. CONCLUSIONS: Our results indicate that expression of 
      Nedd4 promoted cell proliferation and colony formation but prevented apoptosis. 
      Moreover, Nedd4 promoted autophagy and was associated with the mTOR signalling 
      pathway.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Li, Yuyin
AU  - Li Y
AD  - School of Biotechnology, Tianjin University of Science and Technology, Key Lab of 
      Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, 
      300457, China.
FAU - Zhang, Li
AU  - Zhang L
FAU - Zhou, Jie
AU  - Zhou J
FAU - Luo, Shenheng
AU  - Luo S
FAU - Huang, Rui
AU  - Huang R
FAU - Zhao, Changcai
AU  - Zhao C
FAU - Diao, Aipo
AU  - Diao A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150324
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases)
RN  - EC 2.3.2.26 (Nedd4 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acridine Orange/chemistry
MH  - Apoptosis
MH  - Autophagy/*genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Endosomal Sorting Complexes Required for Transport/antagonists & 
      inhibitors/*genetics/metabolism
MH  - Epithelial Cells/*metabolism/pathology
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - HeLa Cells
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Male
MH  - Nedd4 Ubiquitin Protein Ligases
MH  - Permeability
MH  - Prostate/*metabolism/pathology
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
MH  - Ubiquitin-Protein Ligases/antagonists & inhibitors/*genetics/metabolism
PMC - PMC6495840
COIS- None declared.
EDAT- 2015/03/27 06:00
MHDA- 2015/07/16 06:00
PMCR- 2015/03/24
CRDT- 2015/03/27 06:00
PHST- 2014/08/14 00:00 [received]
PHST- 2014/12/11 00:00 [accepted]
PHST- 2015/03/27 06:00 [entrez]
PHST- 2015/03/27 06:00 [pubmed]
PHST- 2015/07/16 06:00 [medline]
PHST- 2015/03/24 00:00 [pmc-release]
AID - CPR12184 [pii]
AID - 10.1111/cpr.12184 [doi]
PST - ppublish
SO  - Cell Prolif. 2015 Jun;48(3):338-47. doi: 10.1111/cpr.12184. Epub 2015 Mar 24.