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Cell Death Differ. 2014 Jan;21(1):146-60. doi: 10.1038/cdd.2013.141. Epub 2013 Oct 18.

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Author information

1
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.

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.

PMID:
24141722
PMCID:
PMC3857621
DOI:
10.1038/cdd.2013.141
[Indexed for MEDLINE]
Free PMC Article

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