RT Journal Article
SR Electronic
T1 What shall we do with the damaged proteins in lung disease? Ask the proteasome!
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj02085-2011
DO 10.1183/09031936.00208511
A1 Silke Meiners
A1 Oliver Eickelberg
YR 2012
UL http://erj.ersjournals.com/content/early/2012/03/22/09031936.00208511.abstract
AB The proteasome constitutes the main protein waste disposal and recycling system of the cell. Together with the endoplasmatic reticulum (ER) stress and the autophagosome pathway, it also takes centre stage in cellular protein quality control. In lung research, the proteasome is – first of all - a promising therapeutic target to intervene with malignant growth of lung cancer cells. Therapeutic targeting of the proteasome has also been extended to pulmonary fibrosis and asthma, using animal models. Moreover, the proteasome is involved in lung pathogenesis: In cystic fibrosis, rapid proteasomal degradation of mutant cystic fibrosis transmembrane regulator contributes to loss of function of lung epithelial cells. In chronic obstructive pulmonary disease (COPD), pulmonary proteasome expression and activity is downregulated and inversely correlates with lung function. In addition, as the proteasome degrades signaling mediators that have been oxidatively modified in COPD, it contributes to further compromise cellular function. The consequences of proteasomal dysfunction are loss of protein quality control, accumulation of misfolded proteins, and exacerbation of cellular stress, which are also hallmarks of protein quality diseases and premature aging. This suggests that proteasome dysfunction can be regarded as a new pathomechanism for chronic lung diseases, awaiting further therapeutic exploration in the future.