상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4

Authors 

Y AhnChae Young HwangS R LeeKi Sun KwonC Lee

Publisher 

Portland Press

Issue Date 

2008

Citation 

Biochemical Journal, vol. 412, no. 2, pp. 331-338

Keywords 

apoptosisdevelopmentally down-regulated gene 4 (Nedd4)feedback regulatorMSneural-precursor-cell-expressedphosphatase and tensin homologue deleted on chromosome 10 (PTEN)transcriptional regulationaffinity chromatographycell deathfeedback control

Abstract 

The tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10; a phosphatidylinositol 3-phosphatase) is a multifunctional protein deregulated in many types of cancer. It is suggested that a number of proteins that relate with PTEN functionally or physically have not yet been found. In order to search for PTEN-interacting proteins that might be crucial in the regulation of PTEN, we exploited a proteomics-based approach. PTEN-expressing NIH 3T3 cell lysates were used in affinity chromatography and then analysed by LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem MS). A total of 93 proteins were identified. Among the proteins identified, we concentrated on the E3 ubiquitin-protein ligase Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated gene 4), and performed subsequent validation experiments using HeLa cells. Nedd4 inhibited PTEN-induced apoptotic cell death and, conversely, the Nedd4 level was down-regulated by PTEN. The down-regulation effect was diminished by a mutation (C124S) in the catalytic site of PTEN. Nedd4 expression was also decreased by a PI3K (phosphoinositide 3-kinase) inhibitor, LY294002, suggesting that the regulation is dependent on the phosphatase-kinase activity of the PTEN-PI3K/Akt pathway. Semi-quantitative real-time PCR analysis revealed that Nedd4 was transcriptionally regulated by PTEN. Thus our results have important implications regarding the roles of PTEN upon the E3 ubquitin ligase Nedd4 as a negative feedback regulator as well as a substrate.

ISSN 

0264-6021

Link 

http://dx.doi.org/10.1042/BJ20071403

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)