Translational Regulation of Autoimmune Inflammation and Lymphoma Genesis by Programmed Cell Death 4
Abstract
Both inflammatory diseases and cancer are associated with heightened protein translation. However, the mechanisms of translational regulation and the roles of translation factors in these diseases are not clear. Programmed cell death 4 (PDCD4) is a newly described inhibitor of protein translation. To determine the roles of PDCD4 in vivo, we generated PDCD4-deficient mice by gene targeting. We report here that mice deficient in PDCD4 develop spontaneous lymphomas and have a significantly reduced life span. Most tumors are of the B lymphoid origin with frequent metastasis to liver and kidney. However, PDCD4-deficient mice are resistant to inflammatory diseases such as autoimmune encephalomyelitis and diabetes. Mechanistic studies reveal that upon activation, PDCD4-deficient lymphocytes preferentially produce cytokines that promote oncogenesis but inhibit inflammation. These results establish that PDCD4 controls lymphoma genesis and autoimmune inflammation by selectively inhibiting protein translation in the immune system.
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Pdcd4 deficient mice develop spontaneous lymphomas, mostly of B lymphoma origin, and have a significantly reduced life span compared with wild type siblings.
“However, the Pdcd4 deficient mice develop spontaneous lymphomas, mostly the B lymphoma origin and have a significantly reduced life span compared with wild type siblings [21].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [21]
PDCD4 may be able to regulate both carcinogenesis and inflammation.
“PDCD4 may be able to regulate both carcinogenesis and inflammation.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [21]
Pdcd4 knockdown mice developed spontaneous tumors, mostly B-lymphoma, and significantly shorter life spans than wild type siblings, but they are resistant to induction of inflammatory diseases such as autoimmune encephalomyelitis and diabetes.
“Pdcd4 knockdown mice developed spontaneous tumors, mostly B-lymphoma and significantly shorter life spans than wild type siblings, but they are resistant to the induction of inflammatory diseases such as autoimmune encephalomyelitis and diabetes [21].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [21]
PDCD4 suppression induces expression of IL-10 and TNFα.
“PDCD4 suppression then induces the expression of IL-10 and TNFα [21,74,75].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [21]
The anti-tumor activity of PDCD4 is documented in Pdcd4 transgenic and knockdown mice.
“and in Pdcd4 transgenic and knockdown mice [21,22].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [21]
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References 36 · Cited by 167
- Authors
- Hilliard, A., Hilliard, B., Zheng, S.-J., Sun, H., Miwa, T., Song, W., Göke, R., & Chen, Y. H.
- Affiliations
- University of Pennsylvania (US)
- Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA 19104
- Department of Pharmacology, School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
- University of Marburg , Marburg ,
- Corresponding author
- Hilliard, Anja
- Hilliard, Brendan
- Sun, Honghong
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-01
- Volume
- 177
- Issue
- 11
- Pages
- 8095-8102
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2115619054
- Cited by
- 167
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 16 · 2015: 8 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI055934, AI-50059, AI 55934)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- PDCD4, translational regulation, protein translation inhibition, lymphoma, autoimmune inflammation, autoimmune encephalomyelitis, diabetes mellitus, B cells, cytokine production, carcinogenesis, metastasis, lifespan
- MeSH terms
- Animals, Autoimmune Diseases, Cell Line, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Inflammation, Lymphocytes, Lymphoma, Mice, Mutant Strains, Protein Biosynthesis, Blotting, Western, Cytokines, RNA-Binding Proteins, Protein Array Analysis, Apoptosis Regulatory Proteins, Mice
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