WWP2 is an E3 ubiquitin ligase for PTEN

Subbareddy Maddika, Sridhar Kavela, Neelam Rani, Vivek Reddy Palicharla, Jenny L. Pokorny, Jann N Sarkaria, Junjie Chen

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

PTEN, a lipid phosphatase, is one of the most frequently mutated tumour suppressors in human cancer. Several recent studies have highlighted the importance of ubiquitylation in regulating PTEN tumour-suppressor function, but the enzymatic machinery required for PTEN ubiquitylation is not clear. In this study, by using a tandem affinity-purification approach, we have identified WWP2 (also known as atrophin-1-interacting protein 2, AIP-2) as a PTEN-interacting protein. WWP2 is an E3 ubiquitin ligase that belongs to the NEDD4-like protein family, which is involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes. We show that WWP2 physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway. Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalNature Cell Biology
Volume13
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Ubiquitin-Protein Ligases
Ubiquitination
Neoplasms
PTEN Phosphohydrolase
Embryonic Stem Cells
Phosphoric Monoester Hydrolases
Cell Survival
Proteins
Apoptosis
T-Lymphocytes
Lipids

ASJC Scopus subject areas

  • Cell Biology

Cite this

Maddika, S., Kavela, S., Rani, N., Palicharla, V. R., Pokorny, J. L., Sarkaria, J. N., & Chen, J. (2011). WWP2 is an E3 ubiquitin ligase for PTEN. Nature Cell Biology, 13(6), 728-733. https://doi.org/10.1038/ncb2240

WWP2 is an E3 ubiquitin ligase for PTEN. / Maddika, Subbareddy; Kavela, Sridhar; Rani, Neelam; Palicharla, Vivek Reddy; Pokorny, Jenny L.; Sarkaria, Jann N; Chen, Junjie.

In: Nature Cell Biology, Vol. 13, No. 6, 06.2011, p. 728-733.

Research output: Contribution to journalArticle

Maddika, S, Kavela, S, Rani, N, Palicharla, VR, Pokorny, JL, Sarkaria, JN & Chen, J 2011, 'WWP2 is an E3 ubiquitin ligase for PTEN', Nature Cell Biology, vol. 13, no. 6, pp. 728-733. https://doi.org/10.1038/ncb2240
Maddika S, Kavela S, Rani N, Palicharla VR, Pokorny JL, Sarkaria JN et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nature Cell Biology. 2011 Jun;13(6):728-733. https://doi.org/10.1038/ncb2240
Maddika, Subbareddy ; Kavela, Sridhar ; Rani, Neelam ; Palicharla, Vivek Reddy ; Pokorny, Jenny L. ; Sarkaria, Jann N ; Chen, Junjie. / WWP2 is an E3 ubiquitin ligase for PTEN. In: Nature Cell Biology. 2011 ; Vol. 13, No. 6. pp. 728-733.
@article{5083d8ca25d54380a64a9f2205e280b0,
title = "WWP2 is an E3 ubiquitin ligase for PTEN",
abstract = "PTEN, a lipid phosphatase, is one of the most frequently mutated tumour suppressors in human cancer. Several recent studies have highlighted the importance of ubiquitylation in regulating PTEN tumour-suppressor function, but the enzymatic machinery required for PTEN ubiquitylation is not clear. In this study, by using a tandem affinity-purification approach, we have identified WWP2 (also known as atrophin-1-interacting protein 2, AIP-2) as a PTEN-interacting protein. WWP2 is an E3 ubiquitin ligase that belongs to the NEDD4-like protein family, which is involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes. We show that WWP2 physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway. Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival.",
author = "Subbareddy Maddika and Sridhar Kavela and Neelam Rani and Palicharla, {Vivek Reddy} and Pokorny, {Jenny L.} and Sarkaria, {Jann N} and Junjie Chen",
year = "2011",
month = "6",
doi = "10.1038/ncb2240",
language = "English (US)",
volume = "13",
pages = "728--733",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - WWP2 is an E3 ubiquitin ligase for PTEN

AU - Maddika, Subbareddy

AU - Kavela, Sridhar

AU - Rani, Neelam

AU - Palicharla, Vivek Reddy

AU - Pokorny, Jenny L.

AU - Sarkaria, Jann N

AU - Chen, Junjie

PY - 2011/6

Y1 - 2011/6

N2 - PTEN, a lipid phosphatase, is one of the most frequently mutated tumour suppressors in human cancer. Several recent studies have highlighted the importance of ubiquitylation in regulating PTEN tumour-suppressor function, but the enzymatic machinery required for PTEN ubiquitylation is not clear. In this study, by using a tandem affinity-purification approach, we have identified WWP2 (also known as atrophin-1-interacting protein 2, AIP-2) as a PTEN-interacting protein. WWP2 is an E3 ubiquitin ligase that belongs to the NEDD4-like protein family, which is involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes. We show that WWP2 physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway. Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival.

AB - PTEN, a lipid phosphatase, is one of the most frequently mutated tumour suppressors in human cancer. Several recent studies have highlighted the importance of ubiquitylation in regulating PTEN tumour-suppressor function, but the enzymatic machinery required for PTEN ubiquitylation is not clear. In this study, by using a tandem affinity-purification approach, we have identified WWP2 (also known as atrophin-1-interacting protein 2, AIP-2) as a PTEN-interacting protein. WWP2 is an E3 ubiquitin ligase that belongs to the NEDD4-like protein family, which is involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes. We show that WWP2 physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway. Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival.

UR - http://www.scopus.com/inward/record.url?scp=79957926724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957926724&partnerID=8YFLogxK

U2 - 10.1038/ncb2240

DO - 10.1038/ncb2240

M3 - Article

C2 - 21532586

AN - SCOPUS:79957926724

VL - 13

SP - 728

EP - 733

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6

ER -