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

S. W. Hong; J. H. Moon; J. S. Kim; J. S. Shin; K. A. Jung; W. K. Lee; S. Y. Jeong; J. J. Hwang; S. J. Lee; Y. A. Suh; I. Kim; K. Y. Nam; S. Han; J. E. Kim; K. P. Kim; Y. S. Hong; J. L. Lee; W. J. Lee; E. K. Choi; J. S. Lee; D. H. Jin; T. W. Kim

doi:10.1038/cdd.2013.141

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

S. W. Hong
, J. H. Moon
, J. S. Kim
, J. S. Shin
, K. A. Jung
, W. K. Lee
, S. Y. Jeong
, J. J. Hwang
, S. J. Lee
, Y. A. Suh
, I. Kim
, K. Y. Nam
, S. Han
, J. E. Kim
, K. P. Kim
, Y. S. Hong
, J. L. Lee
, W. J. Lee
, E. K. Choi
, J. S. Lee

D. H. Jin^*, T. W. Kim

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

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.

Original language	English
Pages (from-to)	146-160
Number of pages	15
Journal	Cell Death and Differentiation
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/cdd.2013.141
Publication status	Published - 2014 Jan
Externally published	Yes

Keywords

NEDD4-1
p34
PTEN
ubiquitination

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/cdd.2013.141

Cite this

Hong, S. W., Moon, J. H., Kim, J. S., Shin, J. S., Jung, K. A., Lee, W. K., Jeong, S. Y., Hwang, J. J., Lee, S. J., Suh, Y. A., Kim, I., Nam, K. Y., Han, S., Kim, J. E., Kim, K. P., Hong, Y. S., Lee, J. L., Lee, W. J., Choi, E. K., ... Kim, T. W. (2014). p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN. Cell Death and Differentiation, 21(1), 146-160. https://doi.org/10.1038/cdd.2013.141

Hong, SW, Moon, JH, Kim, JS, Shin, JS, Jung, KA, Lee, WK, Jeong, SY, Hwang, JJ, Lee, SJ, Suh, YA, Kim, I, Nam, KY, Han, S, Kim, JE, Kim, KP, Hong, YS, Lee, JL, Lee, WJ, Choi, EK, Lee, JS, Jin, DH & Kim, TW 2014, 'p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN', Cell Death and Differentiation, vol. 21, no. 1, pp. 146-160. https://doi.org/10.1038/cdd.2013.141

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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.",

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author = "Hong, \{S. W.\} and Moon, \{J. H.\} and Kim, \{J. S.\} and Shin, \{J. S.\} and Jung, \{K. A.\} and Lee, \{W. K.\} and Jeong, \{S. Y.\} and Hwang, \{J. J.\} and Lee, \{S. J.\} and Suh, \{Y. A.\} and I. Kim and Nam, \{K. Y.\} and S. Han and Kim, \{J. E.\} and Kim, \{K. P.\} and Hong, \{Y. S.\} and Lee, \{J. L.\} and Lee, \{W. J.\} and Choi, \{E. K.\} and Lee, \{J. S.\} and Jin, \{D. H.\} and Kim, \{T. W.\}",

year = "2014",

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doi = "10.1038/cdd.2013.141",

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AU - Kim, J. S.

AU - Shin, J. S.

AU - Jung, K. A.

AU - Lee, W. K.

AU - Jeong, S. Y.

AU - Hwang, J. J.

AU - Lee, S. J.

AU - Suh, Y. A.

AU - Kim, I.

AU - Nam, K. Y.

AU - Han, S.

AU - Kim, J. E.

AU - Kim, K. P.

AU - Hong, Y. S.

AU - Lee, J. L.

AU - Lee, W. J.

AU - Choi, E. K.

AU - Lee, J. S.

AU - Jin, D. H.

AU - Kim, T. W.

PY - 2014/1

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N2 - 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.

AB - 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.

KW - NEDD4-1

KW - p34

KW - PTEN

KW - ubiquitination

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JF - Cell Death and Differentiation

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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