The role of the TRAF-interacting protein in proliferation and differentiation

Exp Dermatol. 2012 May;21(5):321-6. doi: 10.1111/j.1600-0625.2012.01477.x.


Ubiquitination of proteins is a post-translational modification, which decides on the cellular fate of the protein. Addition of ubiquitin moieties to proteins is carried out by the sequential action of three enzymes: E1, ubiquitin-activating enzyme; E2, ubiquitin-conjugating enzyme; and E3, ubiquitin ligase. The TRAF-interacting protein (TRAIP, TRIP, RNF206) functions as Really Interesting New Gene (RING)-type E3 ubiquitin ligase, but its physiological substrates are not yet known. TRAIP was reported to interact with TRAF [tumor necrosis factor (TNF) receptor-associated factors] and the two tumor suppressors CYLD and Syk (spleen tyrosine kinase). Ectopically expressed TRAIP was shown to inhibit nuclear factor-kappa B (NF-κB) signalling. However, recent results suggested a role for TRAIP in biological processes other than NF-κB regulation. Knock-down of TRAIP in human epidermal keratinocytes repressed cellular proliferation and induced a block in the G1/S phase of the cell cycle without affecting NF-κB signalling. TRAIP is necessary for embryonal development as mutations affecting the Drosophila homologue of TRAIP are maternal effect-lethal mutants, and TRAIP knock-out mice die in utero because of aberrant regulation of cell proliferation and apoptosis. These findings underline the tight link between TRAIP and cell proliferation. In this review, we summarize the data on TRAIP and put them into a larger perspective regarding the role of TRAIP in the control of tissue homeostasis.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Proliferation*
  • Embryonic Development / physiology
  • Humans
  • Mice
  • Mice, Knockout
  • NF-kappa B / antagonists & inhibitors
  • Signal Transduction / physiology
  • Skin / cytology
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / physiology*


  • NF-kappa B
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins