Priming the Proteasome to Protect against Proteotoxicity

Xuejun Wang; Hongmin Wang

doi:10.1016/j.molmed.2020.02.007

Priming the Proteasome to Protect against Proteotoxicity

Xuejun Wang, Hongmin Wang

Research output: Contribution to journal › Review article › peer-review

5 Scopus citations

Abstract

Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.

Original language	English (US)
Pages (from-to)	639-648
Number of pages	10
Journal	Trends in Molecular Medicine
Volume	26
Issue number	7
DOIs	https://doi.org/10.1016/j.molmed.2020.02.007
State	Published - Jul 2020
Externally published	Yes

Keywords

cAMP-dependent protein kinase
cGMP-dependent protein kinase
desmin-related cardiomyopathy
phosphodiesterases
proteasome
proteotoxicity

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology

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title = "Priming the Proteasome to Protect against Proteotoxicity",

abstract = "Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.",

keywords = "cAMP-dependent protein kinase, cGMP-dependent protein kinase, desmin-related cardiomyopathy, phosphodiesterases, proteasome, proteotoxicity",

author = "Xuejun Wang and Hongmin Wang",

note = "Funding Information: The work in Dr X. Wang{\textquoteright}s laboratory was supported in part by NIH grants HL072166 , HL085629 , and HL131667 and the work in Dr H. Wang{\textquoteright}s laboratory was supported by NIH grant NS088084 . Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

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doi = "10.1016/j.molmed.2020.02.007",

language = "English (US)",

volume = "26",

pages = "639--648",

journal = "Trends in Molecular Medicine",

issn = "1471-4914",

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TY - JOUR

T1 - Priming the Proteasome to Protect against Proteotoxicity

AU - Wang, Xuejun

AU - Wang, Hongmin

N1 - Funding Information: The work in Dr X. Wang’s laboratory was supported in part by NIH grants HL072166 , HL085629 , and HL131667 and the work in Dr H. Wang’s laboratory was supported by NIH grant NS088084 . Publisher Copyright: © 2020 Elsevier Ltd

PY - 2020/7

Y1 - 2020/7

N2 - Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.

AB - Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.

KW - cAMP-dependent protein kinase

KW - cGMP-dependent protein kinase

KW - desmin-related cardiomyopathy

KW - phosphodiesterases

KW - proteasome

KW - proteotoxicity

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DO - 10.1016/j.molmed.2020.02.007

M3 - Review article

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EP - 648

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

SN - 1471-4914

IS - 7

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Priming the Proteasome to Protect against Proteotoxicity

Abstract

Keywords

ASJC Scopus subject areas

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