Itch inhibition regulates chemosensitivity in vitro

T. M. Hansen, M. Rossi, J. P. Roperch, K. Ansell, K. Simpson, D. Taylor, N. Mathon, R. A. Knight, G. Melino

Research output: Contribution to journalArticle

Abstract

Itch is a member of the HECT family of ubiquitin E3 ligases, and regulates the stability of several proteins involved in response to genotoxic stress. We have previously shown that p73 and p63, two members of the p53 family of tumour suppressors, are targets for Itch-mediated ubiquitylation and degradation. Here, we show that depletion of Itch by RNA interference augments apoptosis upon treatment with chemotherapeutic drugs. We also show that cells with no functional p53 are more sensitive to Itch depletion, highlighting the importance that changes in levels of Itch may play in majority of cancers, where p53 is absent or mutated. Furthermore, reintroduction of Itch in fibroblasts obtained from Itch deficient mice results in reduced cell death upon DNA damage. Overall our findings suggest that inhibition of Itch potentiates the effect of chemotherapeutic drugs revealing the pharmacological potentials of targeting Itch for cancer therapy.

Original languageEnglish
Pages (from-to)33-36
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume361
Issue number1
DOIs
Publication statusPublished - Sep 14 2007

Fingerprint

DNA Damage
Ubiquitin-Protein Ligases
Cell death
Fibroblasts
Pharmaceutical Preparations
Tumors
Neoplasms
Protein Stability
Ubiquitination
RNA
Apoptosis
RNA Interference
Degradation
DNA
Cell Death
Pharmacology
Proteins
In Vitro Techniques
Inhibition (Psychology)
Therapeutics

Keywords

  • Drug discovery
  • E3 ligase
  • Itch
  • p53
  • p53 Chemosensitivity
  • p63
  • p73
  • Proteasome
  • Protein degradation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Itch inhibition regulates chemosensitivity in vitro. / Hansen, T. M.; Rossi, M.; Roperch, J. P.; Ansell, K.; Simpson, K.; Taylor, D.; Mathon, N.; Knight, R. A.; Melino, G.

In: Biochemical and Biophysical Research Communications, Vol. 361, No. 1, 14.09.2007, p. 33-36.

Research output: Contribution to journalArticle

Hansen, TM, Rossi, M, Roperch, JP, Ansell, K, Simpson, K, Taylor, D, Mathon, N, Knight, RA & Melino, G 2007, 'Itch inhibition regulates chemosensitivity in vitro', Biochemical and Biophysical Research Communications, vol. 361, no. 1, pp. 33-36. https://doi.org/10.1016/j.bbrc.2007.06.104
Hansen TM, Rossi M, Roperch JP, Ansell K, Simpson K, Taylor D et al. Itch inhibition regulates chemosensitivity in vitro. Biochemical and Biophysical Research Communications. 2007 Sep 14;361(1):33-36. https://doi.org/10.1016/j.bbrc.2007.06.104
Hansen, T. M. ; Rossi, M. ; Roperch, J. P. ; Ansell, K. ; Simpson, K. ; Taylor, D. ; Mathon, N. ; Knight, R. A. ; Melino, G. / Itch inhibition regulates chemosensitivity in vitro. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 361, No. 1. pp. 33-36.
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