Cargando…

Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation

Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translation...

Descripción completa

Detalles Bibliográficos
Autores principales: Yasuda, Kunihiko, Ohyama, Kyoji, Onga, Kazuko, Kakizuka, Akira, Mori, Nozomu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865000/
https://www.ncbi.nlm.nih.gov/pubmed/24358196
http://dx.doi.org/10.1371/journal.pone.0082523
_version_ 1782295976027881472
author Yasuda, Kunihiko
Ohyama, Kyoji
Onga, Kazuko
Kakizuka, Akira
Mori, Nozomu
author_facet Yasuda, Kunihiko
Ohyama, Kyoji
Onga, Kazuko
Kakizuka, Akira
Mori, Nozomu
author_sort Yasuda, Kunihiko
collection PubMed
description Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translational modification of tropomyosin, which is involved in intracellular sorting of aggregated proteins. We hypothesized that an acetylation complex such as NatB may contribute to protein clearance and/or proteostasis in mammalian cells. Using a poly glutamine (polyQ) aggregation system, we examined whether the NatB complex or its components affect protein aggregation in rat primary cultured hippocampal neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over-expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown (KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly reduced. Although Mdm20 directly associates with Nat5, the overall cellular localization of the two proteins was slightly distinct, and Mdm20 apparently co-localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate appearance of LC3 was evident, suggesting the induction of autophagy. Consistent with this notion, phosphorylation of Akt, most notably at Ser473, was greatly reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called auxiliary subunit of the translation-coupled protein N-acetylation complex, contributes to protein clearance and/or aggregate formation by affecting the phosphorylation level of Akt indepenently from the function of Nat5.
format Online
Article
Text
id pubmed-3865000
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38650002013-12-19 Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation Yasuda, Kunihiko Ohyama, Kyoji Onga, Kazuko Kakizuka, Akira Mori, Nozomu PLoS One Research Article Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translational modification of tropomyosin, which is involved in intracellular sorting of aggregated proteins. We hypothesized that an acetylation complex such as NatB may contribute to protein clearance and/or proteostasis in mammalian cells. Using a poly glutamine (polyQ) aggregation system, we examined whether the NatB complex or its components affect protein aggregation in rat primary cultured hippocampal neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over-expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown (KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly reduced. Although Mdm20 directly associates with Nat5, the overall cellular localization of the two proteins was slightly distinct, and Mdm20 apparently co-localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate appearance of LC3 was evident, suggesting the induction of autophagy. Consistent with this notion, phosphorylation of Akt, most notably at Ser473, was greatly reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called auxiliary subunit of the translation-coupled protein N-acetylation complex, contributes to protein clearance and/or aggregate formation by affecting the phosphorylation level of Akt indepenently from the function of Nat5. Public Library of Science 2013-12-16 /pmc/articles/PMC3865000/ /pubmed/24358196 http://dx.doi.org/10.1371/journal.pone.0082523 Text en © 2013 Yasuda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yasuda, Kunihiko
Ohyama, Kyoji
Onga, Kazuko
Kakizuka, Akira
Mori, Nozomu
Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title_full Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title_fullStr Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title_full_unstemmed Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title_short Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation
title_sort mdm20 stimulates polyq aggregation via inhibiting autophagy through akt-ser473 phosphorylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865000/
https://www.ncbi.nlm.nih.gov/pubmed/24358196
http://dx.doi.org/10.1371/journal.pone.0082523
work_keys_str_mv AT yasudakunihiko mdm20stimulatespolyqaggregationviainhibitingautophagythroughaktser473phosphorylation
AT ohyamakyoji mdm20stimulatespolyqaggregationviainhibitingautophagythroughaktser473phosphorylation
AT ongakazuko mdm20stimulatespolyqaggregationviainhibitingautophagythroughaktser473phosphorylation
AT kakizukaakira mdm20stimulatespolyqaggregationviainhibitingautophagythroughaktser473phosphorylation
AT morinozomu mdm20stimulatespolyqaggregationviainhibitingautophagythroughaktser473phosphorylation