PMID- 27302742
OWN - NLM
STAT- MEDLINE
DCOM- 20180427
LR  - 20201209
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jun 15
TI  - Translational and post-translational regulation of mouse cation transport 
      regulator homolog 1.
PG  - 28016
LID - 10.1038/srep28016 [doi]
LID - 28016
AB  - Cation transport regulator homolog 1 (Chac1) is an endoplasmic reticulum (ER) 
      stress inducible gene that has a function as a gamma-glutamyl cyclotransferase 
      involved in the degradation of glutathione. To characterize the translation and 
      stability of Chac1, we found that the Kozak-like sequence present in the 5' 
      untranslated region (5'UTR) of the Chac1 mRNA was responsible for Chac1 
      translation. In addition, the short form (DeltaChac1), which translated from the 
      second ATG codon, was generated in the absence of the 5'UTR. The proteasome 
      pathway predominantly participated in the stability of the Chac1 protein; 
      however, its expression was remarkably up-regulated by co-transfection with 
      ubiquitin genes. Using an immunoprecipitation assay, we revealed that ubiquitin 
      molecule was directly conjugated to Chac1, and that mutated Chac1 with all lysine 
      residues replaced by arginine was also ubiquitinated. Finally, we showed that WT 
      Chac1 but not DeltaChac1 reduced the intracellular level of glutathione. Taken 
      together, our results suggest that the Chac1 protein expression is regulated in 
      translational and post-translational fashion due to the Kozak-like sequence in 
      the 5'UTR and the ubiquitin-mediated pathways. The bidirectional roles of 
      ubiquitination in regulating Chac1 stabilization might give us a new insight into 
      understanding the homeostasis of glutathione under pathophysiological conditions.
FAU - Nomura, Yuki
AU  - Nomura Y
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
FAU - Hirata, Yoko
AU  - Hirata Y
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
AD  - Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
FAU - Kiuchi, Kazutoshi
AU  - Kiuchi K
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
AD  - Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
FAU - Oh-Hashi, Kentaro
AU  - Oh-Hashi K
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
AD  - Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu 
      University, 1-1 Yanagido, Gifu 501-1193, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160615
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ubiquitin)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 4.3.2.9 (Chac1 protein, mouse)
RN  - EC 4.3.2.9 (gamma-Glutamylcyclotransferase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Animals
MH  - Endoplasmic Reticulum Stress
MH  - Gene Expression Regulation
MH  - Glutathione/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/chemistry/*genetics/*metabolism
MH  - Mice
MH  - Promoter Regions, Genetic
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Biosynthesis
MH  - Protein Processing, Post-Translational
MH  - Protein Stability
MH  - RNA, Messenger/genetics
MH  - Ubiquitin/*metabolism
MH  - Ubiquitination
MH  - gamma-Glutamylcyclotransferase
PMC - PMC4908420
EDAT- 2016/06/16 06:00
MHDA- 2018/04/28 06:00
PMCR- 2016/06/15
CRDT- 2016/06/16 06:00
PHST- 2016/02/14 00:00 [received]
PHST- 2016/05/27 00:00 [accepted]
PHST- 2016/06/16 06:00 [entrez]
PHST- 2016/06/16 06:00 [pubmed]
PHST- 2018/04/28 06:00 [medline]
PHST- 2016/06/15 00:00 [pmc-release]
AID - srep28016 [pii]
AID - 10.1038/srep28016 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jun 15;6:28016. doi: 10.1038/srep28016.