Disruption of IRE1α through its kinase domain attenuates multiple myeloma Article Swipe
Jonathan M. Harnoss
,
Adrien Le Thomas
,
Anna Shemorry
,
Scot A. Marsters
,
David A. Lawrence
,
Min Lu
,
Yung-Chia Ariel Chen
,
Qing Jing
,
Klára Tótpál
,
David Kan
,
Ehud Segal
,
Mark Merchant
,
Mike Reichelt
,
Heidi Ackerly Wallweber
,
Weiru Wang
,
Kevin Clark
,
Susan Kaufman
,
Maureen H. Beresini
,
Steven T. Laing
,
Wendy Sandoval
,
Maria Lorenzo
,
Jian Wu
,
Justin Q. Ly
,
Tom De Bruyn
,
Amy Heidersbach
,
Benjamin Haley
,
Alvin Gogineni
,
Robby M. Weimer
,
Dong Hun Lee
,
Marie-Gabrielle Braun
,
Joachim Rudolph
,
Michael J. VanWyngarden
,
Daniel W. Sherbenou
,
Patricia Gomez‐Bougie
,
Martine Amiot
,
Diego Acosta‐Alvear
,
Peter Walter
,
Avi Ashkenazi
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.1906999116
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.1906999116
Significance Multiple myeloma (MM) is a lethal malignancy arising from plasma cells. MM cells experience endoplasmic reticulum (ER) stress due to immunoglobulin hyperproduction. The ER-resident sensor IRE1α mitigates ER stress by expanding protein-folding and secretion capacity, while supporting proteasomal degradation of ER misfolded proteins. IRE1α elaborates these functions by deploying a cytoplasmic kinase–RNase module to activate the transcription factor XBP1s. Although IRE1α has been implicated in MM, its validity as a potential therapeutic target—particularly as a kinase—has been unclear. Using genetic and pharmacologic disruption, we demonstrate that the IRE1α–XBP1s pathway is critical for MM tumor growth. We further show that the kinase domain of IRE1α is an effective and safe potential small-molecule target for MM therapy.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.1906999116
- https://www.pnas.org/content/pnas/116/33/16420.full.pdf
- OA Status
- bronze
- Cited By
- 111
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2964798481
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2964798481Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1073/pnas.1906999116Digital Object Identifier
- Title
-
Disruption of IRE1α through its kinase domain attenuates multiple myelomaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-08-01Full publication date if available
- Authors
-
Jonathan M. Harnoss, Adrien Le Thomas, Anna Shemorry, Scot A. Marsters, David A. Lawrence, Min Lu, Yung-Chia Ariel Chen, Qing Jing, Klára Tótpál, David Kan, Ehud Segal, Mark Merchant, Mike Reichelt, Heidi Ackerly Wallweber, Weiru Wang, Kevin Clark, Susan Kaufman, Maureen H. Beresini, Steven T. Laing, Wendy Sandoval, Maria Lorenzo, Jian Wu, Justin Q. Ly, Tom De Bruyn, Amy Heidersbach, Benjamin Haley, Alvin Gogineni, Robby M. Weimer, Dong Hun Lee, Marie-Gabrielle Braun, Joachim Rudolph, Michael J. VanWyngarden, Daniel W. Sherbenou, Patricia Gomez‐Bougie, Martine Amiot, Diego Acosta‐Alvear, Peter Walter, Avi AshkenaziList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.1906999116Publisher landing page
- PDF URL
-
https://www.pnas.org/content/pnas/116/33/16420.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://www.pnas.org/content/pnas/116/33/16420.full.pdfDirect OA link when available
- Concepts
-
Multiple myeloma, Cancer research, Kinase, Cell biology, Domain (mathematical analysis), Biology, Immunology, Mathematics, Mathematical analysisTop concepts (fields/topics) attached by OpenAlex
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111Total citation count in OpenAlex
- Citations by year (recent)
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2025: 17, 2024: 10, 2023: 17, 2022: 15, 2021: 27Per-year citation counts (last 5 years)
- References (count)
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53Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.supporting | 37 |
| abstract_inverted_index.ER-resident | 24 |
| abstract_inverted_index.cytoplasmic | 51 |
| abstract_inverted_index.degradation | 39 |
| abstract_inverted_index.demonstrate | 85 |
| abstract_inverted_index.disruption, | 83 |
| abstract_inverted_index.endoplasmic | 15 |
| abstract_inverted_index.proteasomal | 38 |
| abstract_inverted_index.therapeutic | 72 |
| abstract_inverted_index.Significance | 0 |
| abstract_inverted_index.kinase—has | 76 |
| abstract_inverted_index.pharmacologic | 82 |
| abstract_inverted_index.transcription | 57 |
| abstract_inverted_index.IRE1α–XBP1s | 88 |
| abstract_inverted_index.immunoglobulin | 21 |
| abstract_inverted_index.kinase–RNase | 52 |
| abstract_inverted_index.small-molecule | 111 |
| abstract_inverted_index.protein-folding | 32 |
| abstract_inverted_index.hyperproduction. | 22 |
| abstract_inverted_index.target—particularly | 73 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 96 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 38 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.800000011920929 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.9845251 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |