Multifunctional p62 Effects Underlie Diverse Metabolic Diseases

Min Long, Xing Li, Li Li, Matthew Dodson, Donna Zhang, Hongting Zheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders. p62, as a ubiquitin binding protein and selective autophagy substrate, is well established as a key regulator in cancer and neurodegenerative diseases, etc. Recent research on p62 has shown that it may also play an important role in metabolic diseases.p62 possesses multiple domains that regulate a range of metabolic processes, including adipogenesis, inflammation, BAT thermogenesis, insulin signaling, oxidative stress and apoptosis, energy, and nutrient balance. p62 may exert these effects in an autophagy-independent or -dependent manner.Altered expression of p62 in patients with metabolic dysfunctions was observed, and this change has been linked with lipid, glucose and bone metabolism changes in genetically modified animals.p62 participates in the regulation of multiple metabolic diseases, including obesity, T2DM, NAFLD, metabolic bone diseases, gout, atherosclerosis, and thyroid diseases, through regulating its downstream metabolic pathways.

Original languageEnglish (US)
JournalTrends in Endocrinology and Metabolism
DOIs
StateAccepted/In press - 2017

Fingerprint

Metabolic Diseases
Autophagy
Genetically Modified Animals
Gout
Metabolic Bone Diseases
Thyroid Diseases
Ubiquitin
Metabolic Networks and Pathways
Neurodegenerative Diseases
Obesity
Adipogenesis
Thermogenesis
Protein Binding
Immune System
Neoplasms
Atherosclerosis
Carrier Proteins
Oxidative Stress
Insulin
Apoptosis

Keywords

  • Autophagy
  • Autophagy-independent
  • Metabolic diseases
  • P62
  • Sequestosome1 (SQSTM1)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Multifunctional p62 Effects Underlie Diverse Metabolic Diseases. / Long, Min; Li, Xing; Li, Li; Dodson, Matthew; Zhang, Donna; Zheng, Hongting.

In: Trends in Endocrinology and Metabolism, 2017.

Research output: Contribution to journalArticle

Long, Min ; Li, Xing ; Li, Li ; Dodson, Matthew ; Zhang, Donna ; Zheng, Hongting. / Multifunctional p62 Effects Underlie Diverse Metabolic Diseases. In: Trends in Endocrinology and Metabolism. 2017.
@article{8d6f955e5abb44678773d7b3d3d24266,
title = "Multifunctional p62 Effects Underlie Diverse Metabolic Diseases",
abstract = "p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders. p62, as a ubiquitin binding protein and selective autophagy substrate, is well established as a key regulator in cancer and neurodegenerative diseases, etc. Recent research on p62 has shown that it may also play an important role in metabolic diseases.p62 possesses multiple domains that regulate a range of metabolic processes, including adipogenesis, inflammation, BAT thermogenesis, insulin signaling, oxidative stress and apoptosis, energy, and nutrient balance. p62 may exert these effects in an autophagy-independent or -dependent manner.Altered expression of p62 in patients with metabolic dysfunctions was observed, and this change has been linked with lipid, glucose and bone metabolism changes in genetically modified animals.p62 participates in the regulation of multiple metabolic diseases, including obesity, T2DM, NAFLD, metabolic bone diseases, gout, atherosclerosis, and thyroid diseases, through regulating its downstream metabolic pathways.",
keywords = "Autophagy, Autophagy-independent, Metabolic diseases, P62, Sequestosome1 (SQSTM1)",
author = "Min Long and Xing Li and Li Li and Matthew Dodson and Donna Zhang and Hongting Zheng",
year = "2017",
doi = "10.1016/j.tem.2017.09.001",
language = "English (US)",
journal = "Trends in Endocrinology and Metabolism",
issn = "1043-2760",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Multifunctional p62 Effects Underlie Diverse Metabolic Diseases

AU - Long, Min

AU - Li, Xing

AU - Li, Li

AU - Dodson, Matthew

AU - Zhang, Donna

AU - Zheng, Hongting

PY - 2017

Y1 - 2017

N2 - p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders. p62, as a ubiquitin binding protein and selective autophagy substrate, is well established as a key regulator in cancer and neurodegenerative diseases, etc. Recent research on p62 has shown that it may also play an important role in metabolic diseases.p62 possesses multiple domains that regulate a range of metabolic processes, including adipogenesis, inflammation, BAT thermogenesis, insulin signaling, oxidative stress and apoptosis, energy, and nutrient balance. p62 may exert these effects in an autophagy-independent or -dependent manner.Altered expression of p62 in patients with metabolic dysfunctions was observed, and this change has been linked with lipid, glucose and bone metabolism changes in genetically modified animals.p62 participates in the regulation of multiple metabolic diseases, including obesity, T2DM, NAFLD, metabolic bone diseases, gout, atherosclerosis, and thyroid diseases, through regulating its downstream metabolic pathways.

AB - p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders. p62, as a ubiquitin binding protein and selective autophagy substrate, is well established as a key regulator in cancer and neurodegenerative diseases, etc. Recent research on p62 has shown that it may also play an important role in metabolic diseases.p62 possesses multiple domains that regulate a range of metabolic processes, including adipogenesis, inflammation, BAT thermogenesis, insulin signaling, oxidative stress and apoptosis, energy, and nutrient balance. p62 may exert these effects in an autophagy-independent or -dependent manner.Altered expression of p62 in patients with metabolic dysfunctions was observed, and this change has been linked with lipid, glucose and bone metabolism changes in genetically modified animals.p62 participates in the regulation of multiple metabolic diseases, including obesity, T2DM, NAFLD, metabolic bone diseases, gout, atherosclerosis, and thyroid diseases, through regulating its downstream metabolic pathways.

KW - Autophagy

KW - Autophagy-independent

KW - Metabolic diseases

KW - P62

KW - Sequestosome1 (SQSTM1)

UR - http://www.scopus.com/inward/record.url?scp=85030684080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030684080&partnerID=8YFLogxK

U2 - 10.1016/j.tem.2017.09.001

DO - 10.1016/j.tem.2017.09.001

M3 - Article

C2 - 28966079

AN - SCOPUS:85030684080

JO - Trends in Endocrinology and Metabolism

JF - Trends in Endocrinology and Metabolism

SN - 1043-2760

ER -