The interferon regulated ubiquitin-like protein, ISG15, in tumorigenesis: friend or foe?

Cytokine Growth Factor Rev. 2006 Dec;17(6):411-21. doi: 10.1016/j.cytogfr.2006.10.001. Epub 2006 Nov 13.


The interferon-stimulated gene, 15 kDa (ISG15) is an interferon regulated gene that is induced as a primary response to diverse microbial and cell stress stimuli, and encodes the founding member of the ubiquitin-like protein family. ISG15 post-translationally modifies proteins via a pathway parallel to, and partially overlapping with, that of ubiquitin. In addition, ISG15 is released from cells to mediate extracellular cytokine-like activities. Although the biological activities of ISG15 have yet to be fully elucidated, it is clear that ISG15 has the capacity to modulate diverse cellular and physiologic functions. Consistent with this view, alterations in the ISG15 pathway have been identified in human tumors and in tumor cell lines. Here we review evidence of a role for ISG15 as an endogenous tumor suppressor that, when dysregulated in malignant cells, can be subverted to promote oncogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / pharmacology
  • Cytokines / genetics
  • Cytokines / physiology*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Interferons / physiology
  • Models, Biological
  • Molecular Sequence Data
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / genetics
  • Neoplasms / physiopathology
  • Protein Processing, Post-Translational
  • Ubiquitin / genetics
  • Ubiquitin / physiology
  • Ubiquitins / genetics
  • Ubiquitins / physiology*


  • Antineoplastic Agents
  • Cytokines
  • Ubiquitin
  • Ubiquitins
  • ISG15 protein, human
  • Interferons