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WWP1: a versatile ubiquitin E3 ligase in signaling and diseases

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Abstract

WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a multifunction protein containing an N-terminal C2 domain, four tandem WW domains for substrate binding, and a C-terminal catalytic HECT domain for ubiquitin transferring. WWP1 has been suggested to function as the E3 ligase for several PY motif-containing proteins, such as Smad2, KLF5, p63, ErbB4/HER4, RUNX2, JunB, RNF11, SPG20, and Gag, as well as several non-PY motif containing proteins, such as TβR1, Smad4, KLF2, and EPS15. WWP1 regulates a variety of cellular biological processes including protein trafficking and degradation, signaling, transcription, and viral budding. WWP1 has been implicated in several diseases, such as cancers, infectious diseases, neurological diseases, and aging. In this review article, we extensively summarize the current knowledge of WWP1 with special emphasis on the roles and action of mechanism of WWP1 in signaling and human diseases.

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Acknowledgments

This work was supported in part by grants from National Nature Science Foundation of China (81072162 and 81120108019) and a grant from Yunnan Province High-Profile Scientists Program (云南省高端科技人才计划 2010CI114).

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  1. Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China

    Xu Zhi & Ceshi Chen

  2. The Center for Cell Biology and Cancer Research, Albany Medical College, 47, New Scotland Ave., Albany, NY, 12208, USA

    Xu Zhi

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Zhi, X., Chen, C. WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. Cell. Mol. Life Sci. 69, 1425–1434 (2012). https://doi.org/10.1007/s00018-011-0871-7

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