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We have previously shown neuronal cytoplasmic aggregate formation induced by recombinant adenoviruses expressing human wild\u2010type and C\u2010terminal fragment (CTF) TDP\u201043 under the condition of proteasome inhibition\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In the present study, we demonstrated that the formation of the adenoviral TDP\u201043 aggregates was markedly suppressed in rat neural stem cell\u2010derived neuronal cells by co\u2010infection of an adenovirus expressing heat shock transcription factor 1 (HSF1), a master regulator of heat shock response. We performed DNA microarray analysis and searched several candidate molecules, located downstream of HSF1, which counteract TDP\u201043 aggregate formation. Among these, we identified Praja 1 RING\u2010finger E3 ubiquitin ligase (PJA1) as a suppressor of phosphorylation and aggregate formation of TDP\u201043. Co\u2010immunoprecipitation assay revealed that PJA1 binds to CTF TDP\u201043 and the E2\u2010conjugating enzyme UBE2E3. PJA1 also suppressed formation of cytoplasmic phosphorylated TDP\u201043 aggregates in mouse facial motor neurons\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Furthermore, phosphorylated TDP\u201043 aggregates were detected in PJA1\u2010immunoreactive human ALS motor neurons. These results indicate that PJA1 is one of the principal E3 ubiquitin ligases for TDP\u201043 to counteract its aggregation propensity and could be a potential therapeutic target for ALS and FTLD.\n                  <\/jats:p>","DOI":"10.1111\/neup.12694","type":"journal-article","created":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T21:11:16Z","timestamp":1595193076000},"page":"570-586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Praja1\n                    <scp>RING<\/scp>\n                    \u2010finger\n                    <scp>E3<\/scp>\n                    ubiquitin ligase suppresses neuronal cytoplasmic\n                    <scp>TDP<\/scp>\n                    \u201043 aggregate 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