PMID- 31108370
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20231213
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 21
IP  - 7
DP  - 2019 Jul
TI  - SIRT3 regulates cancer cell proliferation through deacetylation of PYCR1 in 
      proline metabolism.
PG  - 665-675
LID - S1476-5586(18)30666-3 [pii]
LID - 10.1016/j.neo.2019.04.008 [doi]
AB  - SIRT3 is a major mitochondrial deacetylase, which regulates various metabolic 
      pathways by deacetylation; however, the effect of SIRT3 on proline metabolism is 
      not reported. Pyrroline-5-carboxylate reductase 1 (PYCR1) participates in proline 
      synthesis process by catalyzing the reduction of P5C to proline with concomitant 
      generation of NAD(+) and NADP(+). PYCR1 is highly expressed in various cancers, 
      and it can promote the growth of tumor cells. Here, through immunoprecipitation 
      and mass spectrometry, we found that PYCR1 is in SIRT3's interacting network. 
      PYCR1 directly binds to SIRT3 both in vivo and in vitro. CBP is the 
      acetyltransferase for PYCR1, whereas SIRT3 deacetylates PYCR1. We further 
      identified that K228 is the major acetylation site for PYCR1. Acetylation of 
      PYCR1 at K228 reduced its enzymatic activity by impairing the formation of the 
      decamer of PYCR1. As a result, acetylation of PYCR1 at K228 inhibits cell 
      proliferation, while deacetylation of PYCR1 mediated by SIRT3 increases PYCR1's 
      activity. Our findings on the regulation of PYCR1 linked proline metabolism with 
      SIRT3, CBP and cell growth, thus providing a potential approach for cancer 
      therapy.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Chen, Shuaiyi
AU  - Chen S
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Yang, Xin
AU  - Yang X
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Yu, Miao
AU  - Yu M
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Wang, Zhe
AU  - Wang Z
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Liu, Boya
AU  - Liu B
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Liu, Minghui
AU  - Liu M
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Liu, Lu
AU  - Liu L
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Ren, Mengmeng
AU  - Ren M
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Qi, Hao
AU  - Qi H
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Zou, Junhua
AU  - Zou J
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China.
FAU - Vucenik, Ivana
AU  - Vucenik I
AD  - Department of Medical and Research Technology, University of Maryland, Baltimore, 
      MD 21201, USA.
FAU - Zhu, Wei-Guo
AU  - Zhu WG
AD  - Department of Biochemistry and Molecular Biology, Shenzhen University School of 
      Medicine, Shenzhen, 518060, China.
FAU - Luo, Jianyuan
AU  - Luo J
AD  - Department of Medical Genetics, Peking University Health Science Center, Beijing, 
      100191, China; Beijing Key Laboratory of Protein Posttranslational Modifications 
      and Cell Function, Department of Biochemistry and Biophysics, Peking University 
      Health Science Center, Beijing 100191, China. Electronic address: 
      luojianyuan@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190517
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Peptide Fragments)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (bone sialoprotein (35-62), human)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.5.1.- (Pyrroline Carboxylate Reductases)
RN  - EC 3.5.1.- (SIRT3 protein, human)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - Acetylation
MH  - Cell Proliferation/genetics
MH  - Humans
MH  - MCF-7 Cells
MH  - Mitochondria/genetics/metabolism
MH  - Neoplasms/*genetics/pathology
MH  - Peptide Fragments/*genetics
MH  - Proline/biosynthesis/metabolism
MH  - Pyrroline Carboxylate Reductases/*genetics
MH  - Sialoglycoproteins/*genetics
MH  - Sirtuin 3/*genetics
MH  - delta-1-Pyrroline-5-Carboxylate Reductase
PMC - PMC6526305
EDAT- 2019/05/21 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/05/17
CRDT- 2019/05/21 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2019/04/23 00:00 [revised]
PHST- 2019/04/24 00:00 [accepted]
PHST- 2019/05/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/05/21 06:00 [entrez]
PHST- 2019/05/17 00:00 [pmc-release]
AID - S1476-5586(18)30666-3 [pii]
AID - 10.1016/j.neo.2019.04.008 [doi]
PST - ppublish
SO  - Neoplasia. 2019 Jul;21(7):665-675. doi: 10.1016/j.neo.2019.04.008. Epub 2019 May 
      17.