Effets cellulaires de l’activation de ligases de l’ubiquitine par la protéine lysosomale LITAF
LITAF (lipopolysaccharide-induced tumor necrosis factor-alpha factor), a lysosomal protein, possesses two PPXY motifs which are able to interact with a specific subgroup comprised of three ubiquitin ligases. These ligases play a role in the ubiquitination and degradation of several cellular proteins in lysosomes and proteasomes. The aim of this study was to show that LITAF activates these ligases and to investigate the consequences of the activation of these ligases on their substrates. To do so, in vivo and in vitro ubiquitination assays were conducted in the presence of LITAF and the appropriate ligases and substrates. Activation of the ligases was measured by their self-ubiquitination rate and activation of their substrates was measured by their ubiquitination and degradation rates. Our results show that the activity of the ligases is increased in the presence of LITAF and that ubiquitination and degradation of the substrates are partially increased. Thus, LITAF might play a role in the regulation of ubiquitin ligases. The importance of these results lies in the fact that expression and intracellular localization of LITAF are affected in several pathologies. Our results bring new insights into the physiological role of this protein and could partly explain how the altered expression of LITAF affects cellular balance.
LITAF Lysosome Ligase Itch WWP1 Charcot-Marie-Tooth Ubiquitin Endosomal trafficking