Rab5 and Ndfip1 Are Involved in Pten Ubiquitination and Nuclear Trafficking

Li, Yijia, Low, Ley-Hian, Putz, Ulrich, Goh, Choo-Peng, Tan, Seong-Seng and Howitt, Jason (2014) Rab5 and Ndfip1 Are Involved in Pten Ubiquitination and Nuclear Trafficking. Traffic, 15 7: 749-761. doi:10.1111/tra.12175

Author Li, Yijia
Low, Ley-Hian
Putz, Ulrich
Goh, Choo-Peng
Tan, Seong-Seng
Howitt, Jason
Title Rab5 and Ndfip1 Are Involved in Pten Ubiquitination and Nuclear Trafficking
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.1111/tra.12175
Open Access Status
Volume 15
Issue 7
Start page 749
End page 761
Total pages 13
Place of publication Malden, MA United States
Publisher Wiley-Blackwell Publishing
Collection year 2015
Language eng
Abstract The spatial regulation of Pten is critical for its role as a tumour suppressor with both nuclear and cytoplasmic locations being implicated with distinct functions. In the cytoplasm, Pten plays a central role in opposing PI3K/Akt cell signalling, whereas in the nucleus, Pten is important for maintaining genome stability and enhancing the tumour suppressor activity of APC-CDH1. Despite this diversity in protein function at different subcellular locations, there is limited knowledge on how Pten is able to find different cellular niches. Here, we report that Rab5 GTPase is required for efficient trafficking and ubiquitination of Pten on endosomes inside the cytosol. Using bimolecular fluorescence complementation (BiFC) for imaging protein interactions, we observed that ubiquitinated Pten is localized to peri-nuclear and nuclear regions of the cell. Nuclear trafficking of Pten required both Rab5 as well as the E3 ligase adaptor protein Ndfip1. Rab5 colocalization with Pten was observed on endosomes and expression of a dominant negative form of Rab5 significantly reduced Pten ubiquitination and nuclear trafficking. Genomic deletion of Ndfip1 abrogated nuclear trafficking of ubiquitinated Pten, even in the presence of Rab5. Our findings show that endosomal trafficking and ubiquitination are important mechanisms for the subcellular distribution of Pten. The subcellular distribution of Pten is critical for its multiple roles as a tumour suppressor. Here we describe the trafficking of Pten on both early and recycling endosomes using bimolecular fluorescence complementation. We show that both Rab5 GTPase and the E3 ligase adaptor protein Ndfip1 are required for ubiquitination and nuclear trafficking of Pten.
Keyword Cancer
Ubiquitin ligase
Vesicular trafficking
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Mon, 27 Oct 2014, 17:04:53 EST by Sylvie Pichelin on behalf of Queensland Brain Institute