title: Formation of distinct inclusion bodies by inhibition of ubiquitin-proteasome and autophagy-lysosome pathways.
abstract: Accumulation of misfolded proteins is caused by the impairment of protein quality control systems, such as ubiquitin-proteasome pathway (UPP) and autophagy-lysosome pathway (ALP). In this study, the formation of inclusion bodies was examined after the blockade of UPP and/or ALP in A549 cells. UPP inhibition induced a single and large inclusion body localized in microtubule-organizing center. Interestingly, however, ALP inhibition generated dispersed small inclusion bodies in the cytoplasm. Tuberous sclerosis complex 2 was selectively accumulated in the inclusion bodies of UPP-inhibited cells, but not those of ALP-inhibited cells. Blockade of transcription and translation entirely inhibited the formation of inclusion body induced by UPP inhibition, but partially by ALP inhibition. Moreover, the simultaneous inhibition of two protein catabolic pathways independently developed two distinct inclusion bodies within a single cell. These findings clearly demonstrated that dysfunction of each catabolic pathway induced formation and accumulation of unique inclusion bodies on the basis of morphology, localization and formation process in A549 cells.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon 305-701, Republic of Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Lee
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Yang
authors.forename: Cheol O
authors.initials: CO
authors.lastname: Joe
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
mesh_terms: D001343:Autophagy; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes; D019636:Neurodegenerative Diseases / Q000378:metabolism; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D025801:Ubiquitin / Q000037:antagonists & inhibitors*
chemical_list: D061988:Proteasome Inhibitors; D025801:Ubiquitin