The roles of ubiquitin modifying enzymes in neoplastic disease

Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):456-483. doi: 10.1016/j.bbcan.2017.09.002. Epub 2017 Sep 18.


The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses. In this review, we highlight the known oncogenic and tumour suppressive effects of ubiquitin modifying enzymes in cancer relevant pathways with specific focus on PI3K, MAPK, TGFβ, WNT, and YAP pathways. Moreover, we discuss the capacity of targeting DUBs as a novel anticancer therapeutic strategy.

Keywords: Cancer; Deubiquitinating enzymes; Dub inhibitors; E3 ligases; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Deubiquitinating Enzymes / antagonists & inhibitors
  • Deubiquitinating Enzymes / physiology
  • Humans
  • MAP Kinase Signaling System / physiology
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Nuclear Proteins / physiology
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Smad Proteins / physiology
  • Transcription Factors / physiology
  • Transforming Growth Factor beta / physiology
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / physiology
  • Wnt Signaling Pathway / physiology


  • Cell Cycle Proteins
  • Nuclear Proteins
  • Smad Proteins
  • Transcription Factors
  • Transforming Growth Factor beta
  • Ubiquitin
  • YY1AP1 protein, human
  • SMURF2 protein, human
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • Deubiquitinating Enzymes