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Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death.

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Title: Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death.
Authors: Wei Wang1, Hawkridge, Adam M.2, Yibao Ma1, Bei Zhang3, Mangrum, John B.2, Hassan, Zaneera H.2, Tianhai He1, Blat, Sofiya1, Chunqing Guo4, Huiping Zhou5,6, Jinze Liu3, Xiang-Yang Wang4,5,6, Xianjun Fang1 xianjun.fang@vcuhealth.org
Source: Journal of Biological Chemistry. Jul2023, Vol. 299 Issue 7, p1-14. 14p.
Subjects: Cell death, Unfolded protein response, Mitochondrial proteins, Liver cells, Cancer cells, Sudden death, Cancer cell culture
Abstract: Biological functions of the highly conserved ubiquitin-like protein 5 (UBL5) are not well understood. In Caenorhabditis elegans, UBL5 is induced under mitochondrial stress to mount the mitochondrial unfolded protein response (UPR). However, the role of UBL5 in the more prevalent endoplasmic reticulum (ER) stress-UPR in the mammalian system is unknown. In the present work, we demonstrated that UBL5 was an ER stress-responsive protein, undergoing rapid depletion in mammalian cells and livers of mice. The ER stress-induced UBL5 depletion was mediated by proteasome-dependent yet ubiquitin-independent proteolysis. Activation of the protein kinase R-like ER kinase arm of the UPR was essential and sufficient for inducing UBL5 degradation. RNA-Seq analysis of UBL5-regulated transcriptome revealed that multiple death pathways were activated in UBL5-silenced cells. In agreement with this, UBL5 knockdown induced severe apoptosis in culture and suppressed tumorigenicity of cancer cells in vivo. Furthermore, overexpression of UBL5 protected specifically against ER stress-induced apoptosis. These results identify UBL5 as a physiologically relevant survival regulator that is proteolytically depleted by the UPR-protein kinase R-like ER kinase pathway, linking ER stress to cell death. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 169843243
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death.
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  Data: <searchLink fieldCode="AR" term="%22Wei+Wang%22">Wei Wang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Hawkridge%2C+Adam+M%2E%22">Hawkridge, Adam M.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Yibao+Ma%22">Yibao Ma</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Bei+Zhang%22">Bei Zhang</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Mangrum%2C+John+B%2E%22">Mangrum, John B.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Hassan%2C+Zaneera+H%2E%22">Hassan, Zaneera H.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Tianhai+He%22">Tianhai He</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Blat%2C+Sofiya%22">Blat, Sofiya</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chunqing+Guo%22">Chunqing Guo</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Huiping+Zhou%22">Huiping Zhou</searchLink><relatesTo>5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Jinze+Liu%22">Jinze Liu</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Xiang-Yang+Wang%22">Xiang-Yang Wang</searchLink><relatesTo>4,5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Xianjun+Fang%22">Xianjun Fang</searchLink><relatesTo>1</relatesTo><i> xianjun.fang@vcuhealth.org</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Jul2023, Vol. 299 Issue 7, p1-14. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Cell+death%22">Cell death</searchLink><br /><searchLink fieldCode="DE" term="%22Unfolded+protein+response%22">Unfolded protein response</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+proteins%22">Mitochondrial proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+cells%22">Liver cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+cells%22">Cancer cells</searchLink><br /><searchLink fieldCode="DE" term="%22Sudden+death%22">Sudden death</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+cell+culture%22">Cancer cell culture</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Biological functions of the highly conserved ubiquitin-like protein 5 (UBL5) are not well understood. In Caenorhabditis elegans, UBL5 is induced under mitochondrial stress to mount the mitochondrial unfolded protein response (UPR). However, the role of UBL5 in the more prevalent endoplasmic reticulum (ER) stress-UPR in the mammalian system is unknown. In the present work, we demonstrated that UBL5 was an ER stress-responsive protein, undergoing rapid depletion in mammalian cells and livers of mice. The ER stress-induced UBL5 depletion was mediated by proteasome-dependent yet ubiquitin-independent proteolysis. Activation of the protein kinase R-like ER kinase arm of the UPR was essential and sufficient for inducing UBL5 degradation. RNA-Seq analysis of UBL5-regulated transcriptome revealed that multiple death pathways were activated in UBL5-silenced cells. In agreement with this, UBL5 knockdown induced severe apoptosis in culture and suppressed tumorigenicity of cancer cells in vivo. Furthermore, overexpression of UBL5 protected specifically against ER stress-induced apoptosis. These results identify UBL5 as a physiologically relevant survival regulator that is proteolytically depleted by the UPR-protein kinase R-like ER kinase pathway, linking ER stress to cell death. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.jbc.2023.104915
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 1
    Subjects:
      – SubjectFull: Cell death
        Type: general
      – SubjectFull: Unfolded protein response
        Type: general
      – SubjectFull: Mitochondrial proteins
        Type: general
      – SubjectFull: Liver cells
        Type: general
      – SubjectFull: Cancer cells
        Type: general
      – SubjectFull: Sudden death
        Type: general
      – SubjectFull: Cancer cell culture
        Type: general
    Titles:
      – TitleFull: Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death.
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            NameFull: Wei Wang
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            – D: 01
              M: 07
              Text: Jul2023
              Type: published
              Y: 2023
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            – TitleFull: Journal of Biological Chemistry
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