PMID- 24358196
OWN - NLM
STAT- MEDLINE
DCOM- 20140930
LR  - 20230111
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Mdm20 stimulates polyQ aggregation via inhibiting autophagy through Akt-Ser473 
      phosphorylation.
PG  - e82523
LID - 10.1371/journal.pone.0082523 [doi]
LID - e82523
AB  - 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.
FAU - Yasuda, Kunihiko
AU  - Yasuda K
AD  - From the Department of Anatomy and Neurobiology, Nagasaki University School of 
      Medicine, Nagasaki, Japan.
FAU - Ohyama, Kyoji
AU  - Ohyama K
AD  - From the Department of Anatomy and Neurobiology, Nagasaki University School of 
      Medicine, Nagasaki, Japan.
FAU - Onga, Kazuko
AU  - Onga K
AD  - From the Department of Anatomy and Neurobiology, Nagasaki University School of 
      Medicine, Nagasaki, Japan.
FAU - Kakizuka, Akira
AU  - Kakizuka A
AD  - Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, 
      Kyoto, Japan.
FAU - Mori, Nozomu
AU  - Mori N
AD  - From the Department of Anatomy and Neurobiology, Nagasaki University School of 
      Medicine, Nagasaki, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131216
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Peptides)
RN  - 26700-71-0 (polyglutamine)
RN  - EC 2.3.1.255 (N-Terminal Acetyltransferase B)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
ECI - PLoS One. 2023 Jan 11;18(1):e0279152. PMID: 36630328
MH  - Animals
MH  - Autophagy/*physiology
MH  - HEK293 Cells
MH  - Hippocampus/metabolism
MH  - Humans
MH  - N-Terminal Acetyltransferase B/*metabolism
MH  - Neurons/*metabolism
MH  - Peptides/*metabolism
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC3865000
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/21 06:00
MHDA- 2014/10/01 06:00
PMCR- 2013/12/16
CRDT- 2013/12/21 06:00
PHST- 2013/08/06 00:00 [received]
PHST- 2013/10/24 00:00 [accepted]
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/10/01 06:00 [medline]
PHST- 2013/12/16 00:00 [pmc-release]
AID - PONE-D-13-32281 [pii]
AID - 10.1371/journal.pone.0082523 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 16;8(12):e82523. doi: 10.1371/journal.pone.0082523. 
      eCollection 2013.