Source: International Congress 2014 – Cell biology 2014

Abstract

Protein homeostasis is mainly regulated by the proteasome playing an essential role in cellular signaling and immune response. The 20S core particle of the proteasome encloses two sets of three active sites. Upon inflammation, expression of immuno-catalytic subunits is induced. Combinations of standard and immuno-subunits result in formation of constitutive, mixed and immuno-proteasomes. To become fully activated, the 20S core associates with regulatory particles. Whereas catalytic subunits control cleavage specificity, regulators modulate substrate specificity and turnover. Of note, proteasome composition is organ-, cell-, and cell compartment-specific. While changes in proteasome composition are known to be involved in diseases in several organs, they were never studied in the lung.Here, we provide a comprehensive description of the different proteasome complexes in the lung. For that, we isolated proteasome complexes from whole lung homogenates and from A549 cells. A first round of mass spectrometry analyses allowed us to identify all proteasome subunits and regulators, as well as new proteasome interacting proteins. In addition, we characterized several unreported prost-translational modifications (PTM). Currently, we are validating our newly identified proteasome interactors and the role of PTMs for proteasome function. In particular, we are focusing on a new deuibiquitinase, known to be down-regulated in lung cancer; a thioredoxin-like domain protein; and ribosomal subunits.This study will help us to understand the possible involvement of proteasome function in the development of lung diseases, and contributes to the identification of novel therapeutic targets that regulate protein homeostasis.

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Citations should be made in the following way:
A. Caniard, J. Merl, S. Hauck, O. Eickelberg, S. Meiners (Munich, Germany). Comprehensive characterization of the lung proteasome. Eur Respir J 2014; 44: Suppl. 58, 3860

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