PMID- 29425493
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20211001
IS  - 2211-1247 (Electronic)
VI  - 22
IP  - 6
DP  - 2018 Feb 6
TI  - Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity.
PG  - 1365-1373
LID - S2211-1247(18)30062-7 [pii]
LID - 10.1016/j.celrep.2018.01.030 [doi]
AB  - Lysine succinylation was recently identified as a post-translational modification 
      in cells. However, the molecular mechanism underlying lysine succinylation 
      remains unclear. Here, we show that carnitine palmitoyltransferase 1A (CPT1A) has 
      lysine succinyltransferase (LSTase) activity in vivo and in vitro. Using a stable 
      isotope labeling by amino acid in cell culture (SILAC)-based proteomics approach, 
      we found that 101 proteins were more succinylated in cells expressing wild-type 
      (WT) CPT1A compared with vector control cells. One of the most heavily 
      succinylated proteins in this analysis was enolase 1. We found that CPT1A WT 
      succinylated enolase 1 and reduced enolase enzymatic activity in cells and 
      in vitro. Importantly, mutation of CPT1A Gly710 (G710E) selectively inactivated 
      carnitine palmitoyltransferase (CPTase) activity but not the LSTase activity that 
      decreased enolase activity in cells and promoted cell proliferation under 
      glutamine depletion. These findings suggest that CPT1A acts as an LSTase that can 
      regulate enzymatic activity of a substrate protein and metabolism independent of 
      its classical CPTase activity.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kurmi, Kiran
AU  - Kurmi K
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, 
      Mayo Clinic, Rochester, MN 55905, USA.
FAU - Hitosugi, Sadae
AU  - Hitosugi S
AD  - Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Wiese, Elizabeth K
AU  - Wiese EK
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, 
      Mayo Clinic, Rochester, MN 55905, USA.
FAU - Boakye-Agyeman, Felix
AU  - Boakye-Agyeman F
AD  - Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Gonsalves, Wilson I
AU  - Gonsalves WI
AD  - Department of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Lou, Zhenkun
AU  - Lou Z
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Division of Oncology Research, Mayo Clinic, Rochester, 
      MN 55905, USA.
FAU - Karnitz, Larry M
AU  - Karnitz LM
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Division of Oncology Research, Mayo Clinic, Rochester, 
      MN 55905, USA.
FAU - Goetz, Matthew P
AU  - Goetz MP
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Division of Medical Oncology, Mayo Clinic, Rochester, 
      MN 55905, USA.
FAU - Hitosugi, Taro
AU  - Hitosugi T
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN 55905, USA; Division of Oncology Research, Mayo Clinic, Rochester, 
      MN 55905, USA. Electronic address: hitosugi.taro@mayo.edu.
LA  - eng
GR  - P50 CA116201/CA/NCI NIH HHS/United States
GR  - T32 GM072474/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Carnitine O-Palmitoyltransferase/*metabolism
MH  - Humans
MH  - Lysine/*metabolism
MH  - Protein Processing, Post-Translational/*physiology
PMC - PMC5826573
MID - NIHMS943494
OTO - NOTNLM
OT  - CPT1A
OT  - carnitine palmitoyltransferase 1A
OT  - lysine succinylation
OT  - lysine succinyltransferase
OT  - metabolism
OT  - post-translational modification
OT  - signal transduction
OT  - succinyl-CoA
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2018/02/10 06:00
MHDA- 2019/05/21 06:00
PMCR- 2018/02/26
CRDT- 2018/02/10 06:00
PHST- 2017/08/25 00:00 [received]
PHST- 2017/12/26 00:00 [revised]
PHST- 2018/01/09 00:00 [accepted]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2018/02/10 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/02/26 00:00 [pmc-release]
AID - S2211-1247(18)30062-7 [pii]
AID - 10.1016/j.celrep.2018.01.030 [doi]
PST - ppublish
SO  - Cell Rep. 2018 Feb 6;22(6):1365-1373. doi: 10.1016/j.celrep.2018.01.030.