Ubiquitin ligase Itch regulates p38α and skin inflammation | 8726
Journal of Clinical & Experimental Dermatology Research

Journal of Clinical & Experimental Dermatology Research
Open Access

ISSN: 2155-9554

+44 7868 792050

Ubiquitin ligase Itch regulates p38α and skin inflammation via ubiquitination of Tab1

International Conference on Psoriasis and Skin Specialists Meeting

December 08-09, 2016 Dallas, USA

Venuprasad Poojary

Baylor Research Institute, USA

Scientific Tracks Abstracts: J Clin Exp Dermatol Res

Abstract :

Deficiency of the ubiquitin ligase Itch causes a scratching â�?�?Itchyâ�?�? phenotype. However, the precise molecular mechanisms by which Itch regulates skin inflammation remain unclear. We have found elevated activation of the kinase p38�?± in the spontaneous and experimentally induced skin lesions of Itch-/- mice. Mechanistically, we demonstrate that Itch binds directly to Tab1 via the conserved PPXY motif and negatively regulates p38�?±. ShRNA-mediated inhibition of Tab1 attenuated the prolonged p38�?± phosphorylation seen in Itch-/- cells. Similarly, reconstitution of WT Itch but not the Itch-C830A mutant (which lacks the ligase activity) inhibited p38�?± phosphorylation in Itch-/- cells. Since Itch-deficient mice are unable to regulate Tab1 and p38�?±, elevated levels of pro-inflammatory cytokines including TNF, IL-6, IL-1�?², IL-11 and IL-19 were observed in the skin. Inhibition of p38 or blocking the interaction of p38�?± with Tab1 using a cell-permeable peptide dramatically attenuated skin inflammation in Itch-/- mice. These results provide new insights into how Itch-mediated regulatory mechanisms prevent chronic skin inflammation, which could be exploited therapeutically in chronic inflammatory skin diseases.

Biography :

Venuprasad Poojary has completed his PhD in Immunology at the National Center for Cell Science, Pune, India and Postdoctoral studies from La Jolla Institute for Allergy Immunology in San Diego, CA. He is an Associate Investigator at the Baylor Institute for Immunology Research in Dallas, TX. He has published more than 25 papers in reputed journals.