Song, Eun Joo Hong, Hye-Min Yoo, Young Sook 2024-01-20T21:36:22Z 2024-01-20T21:36:22Z 2021-09-03 2009-03 1357-2725 https://pubs.kist.re.kr/handle/201004/132695 The ubiquitin-proteasome pathway regulates many biological processes, including protein degradation. receptor endocytosis, protein sorting, sub nuclear trafficking and neuronal differentiation. While proteasome inhibition is known to induce neurite outgrowth, the signaling mechanisms that mediate these effects have not been defined. In this study, we investigated the underlying mechanisms that link proteasome inhibition with neurite generation. We found that the proteasome inhibitors, MG 132 and lactacystin, induced neurite out growth and also activated extracellular signal-regulated kinase/mitogen activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways. These proteasome inhibitors also induced phosphorylation and ubiquitination of TrkA receptors, indicating that proteasome inhibition activates the major pathways of TrkA signaling. However, in contrast to nerve growth factor stimulation, which induces internalization of surface TrkA receptors, proteasome inhibitor-induced neurite outgrowth did not require TrkA receptor internalization. These results indicate that the ubiquitin-proteasome system regulates neurite formation through posttranslational modification of TrkA receptors. (C) 2008 Published by Elsevier Ltd. English PERGAMON-ELSEVIER SCIENCE LTD NEUROTROPHIN RECEPTORS UBIQUITIN SURVIVAL TRAFFICKING ROLES TRANSACTIVATION INTERNALIZATION LACTACYSTIN ACTIVATION RESPONSES Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor Article 10.1016/j.biocel.2008.04.022 1 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v.41, no.3, pp.539 - 545 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 41 3 539 545 scie scopus 000263195800019 2-s2.0-58149295811 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article NEUROTROPHIN RECEPTORS UBIQUITIN SURVIVAL TRAFFICKING ROLES TRANSACTIVATION INTERNALIZATION LACTACYSTIN ACTIVATION RESPONSES Neurite outgrowth Proteasome inhibitor TrkA receptor MG132 Ubiquitination