Epidermal growth factor receptor substrate 15 (Protein Eps15) (Protein AF-1p) [AF1P]

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WWP1: a versatile ubiquitin E3 ligase in signaling and diseases.

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.

MeSH Terms

  • Aging
  • ErbB Receptors
  • Gene Expression
  • Humans
  • Infections
  • Kruppel-Like Transcription Factors
  • Neoplasms
  • Nervous System Diseases
  • Protein Structure, Tertiary
  • Signal Transduction
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases
  • Ubiquitination