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Publication : Itch inhibition regulates chemosensitivity in vitro.

First Author  Hansen TM Year  2007
Journal  Biochem Biophys Res Commun Volume  361
Issue  1 Pages  33-6
PubMed ID  17640619 Mgi Jnum  J:123488
Mgi Id  MGI:3718732 Doi  10.1016/j.bbrc.2007.06.104
Citation  Hansen TM, et al. (2007) Itch inhibition regulates chemosensitivity in vitro. Biochem Biophys Res Commun 361(1):33-6
abstractText  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.
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