Posttranslational regulation of PGC‐1α and its implication in cancer metabolism

Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator‐activated receptor γ coactivator 1a (PGC‐1α), which serves as a master...

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Published inInternational journal of cancer Vol. 145; no. 6; pp. 1475 - 1483
Main Authors Luo, Xiangjian, Liao, Chaoliang, Quan, Jing, Cheng, Can, Zhao, Xu, Bode, Ann M., Cao, Ya
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 15.09.2019
Wiley Subscription Services, Inc
Subjects
Acetylation
Autophagy
Cancer
cancer metabolism
Energy metabolism
Humans
Localization
Malignancy
Medical research
Metabolism
Methylation
Mini Review
Mini Reviews
Mitochondria
Mitochondria - metabolism
Mitophagy
Neoplasms - metabolism
Organelles
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - chemistry
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
PGC‐1α
Phosphorylation
posttranslational modifications
Protein Conformation
Protein Processing, Post-Translational
Signal Transduction
Therapeutic applications
Transcription
Tumorigenesis
Ubiquitination
cancer metabolism
PGC-1α
posttranslational modifications
Online AccessGet full text
ISSN0020-7136
1097-0215
1097-0215
DOI10.1002/ijc.32253

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Abstract Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator‐activated receptor γ coactivator 1a (PGC‐1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC‐1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC‐1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC‐1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC‐1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC‐1α modulators. A better understanding of the elegant function of PGC‐1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC‐1α signaling.
AbstractList Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator‐activated receptor γ coactivator 1a (PGC‐1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC‐1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC‐1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC‐1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC‐1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC‐1α modulators. A better understanding of the elegant function of PGC‐1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC‐1α signaling.
Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor γ coactivator 1a (PGC-1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1α modulators. A better understanding of the elegant function of PGC-1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1α signaling.Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor γ coactivator 1a (PGC-1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1α modulators. A better understanding of the elegant function of PGC-1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1α signaling.
Author Quan, Jing
Zhao, Xu
Cao, Ya
Luo, Xiangjian
Liao, Chaoliang
Cheng, Can
Bode, Ann M.
AuthorAffiliation 4 Molecular Imaging Research Center of Central South University Changsha Hunan 410078 China
5 The Hormel Institute University of Minnesota Austin MN 55912 USA
1 Key Laboratory of Carcinogenesis and Invasion Chinese Ministry of Education, Xiangya Hospital, Central South University Changsha Hunan 410078 China
2 Cancer Research Institute and School of Basic Medical Science, Central South University Changsha Hunan 410078 China
3 Key Laboratory of Carcinogenesis Chinese Ministry of Health Changsha Hunan 410078 China
AuthorAffiliation_xml – name: 2 Cancer Research Institute and School of Basic Medical Science, Central South University Changsha Hunan 410078 China
– name: 5 The Hormel Institute University of Minnesota Austin MN 55912 USA
– name: 1 Key Laboratory of Carcinogenesis and Invasion Chinese Ministry of Education, Xiangya Hospital, Central South University Changsha Hunan 410078 China
– name: 3 Key Laboratory of Carcinogenesis Chinese Ministry of Health Changsha Hunan 410078 China
– name: 4 Molecular Imaging Research Center of Central South University Changsha Hunan 410078 China
Author_xml – sequence: 1
  givenname: Xiangjian
  orcidid: 0000-0003-0124-8799
  surname: Luo
  fullname: Luo, Xiangjian
  email: luocsu@csu.edu.cn
  organization: Molecular Imaging Research Center of Central South University
– sequence: 2
  givenname: Chaoliang
  surname: Liao
  fullname: Liao, Chaoliang
  organization: Chinese Ministry of Health
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  givenname: Jing
  surname: Quan
  fullname: Quan, Jing
  organization: Chinese Ministry of Health
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  givenname: Can
  surname: Cheng
  fullname: Cheng, Can
  organization: Chinese Ministry of Health
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  fullname: Zhao, Xu
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  organization: University of Minnesota
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  givenname: Ya
  surname: Cao
  fullname: Cao, Ya
  organization: Molecular Imaging Research Center of Central South University
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Issue 6
Keywords cancer metabolism
PGC-1α
posttranslational modifications
Language English
License Attribution-NonCommercial
2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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C.L. and J.Q. contributed equally to this work
Conflict of interest: No potential conflicts of interest were disclosed.
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Snippet Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism....
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SubjectTerms Acetylation
Autophagy
Cancer
cancer metabolism
Energy metabolism
Humans
Localization
Malignancy
Medical research
Metabolism
Methylation
Mini Review
Mini Reviews
Mitochondria
Mitochondria - metabolism
Mitophagy
Neoplasms - metabolism
Organelles
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - chemistry
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
PGC‐1α
Phosphorylation
posttranslational modifications
Protein Conformation
Protein Processing, Post-Translational
Signal Transduction
Therapeutic applications
Transcription
Tumorigenesis
Ubiquitination
Title Posttranslational regulation of PGC‐1α and its implication in cancer metabolism
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fijc.32253
https://www.ncbi.nlm.nih.gov/pubmed/30848477
https://www.proquest.com/docview/2259861403
https://www.proquest.com/docview/2189543496
https://pubmed.ncbi.nlm.nih.gov/PMC6767394
Volume 145
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