The API2–MALT1 fusion exploits TNFR pathway-associated RIP1 ubiquitination to promote oncogenic NF-κB signaling
Open accessAbstract
The API2-MALT1 fusion oncoprotein is created by the recurrent t(11;18)(q21;q21) chromosomal translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. We identified receptor interacting protein-1 (RIP1) as a novel API2-MALT1-associated protein, and demonstrate that RIP1 is required for API2-MALT1 to stimulate canonical nuclear factor kappa B (NF-κB). API2-MALT1 promotes ubiquitination of RIP1 at lysine (K) 377, which is necessary for full NF-κB activation. Furthermore, we found that TNF receptor-associated factor 2 (TRAF2) recruitment is required for API2-MALT1 to induce RIP1 ubiquitination, NF-κB activation and cellular transformation. Although both TRAF2 and RIP1 interact with the API2 moiety of API2-MALT1, this moiety alone is insufficient to induce RIP1 ubiquitination or activate NF-κB, indicating that API2-MALT1-dependent RIP1 ubiquitination represents a gain of function requiring the concerted actions of both the API2 and MALT1 moieties of the fusion. Intriguingly, constitutive RIP1 ubiquitination was recently demonstrated in several solid tumors, and now our study implicates RIP1 ubiquitination as a critical component of API2-MALT1-dependent lymphomagenesis.
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BIRC3 is highly expressed in many hematologic malignant cells, such as CLL, MCL, FL, MZL, SMZL, and DLBCL, compared to other IAP family proteins.
“it is highly expressed in many hematologic malignant cells, such as CLL, MCL, follicular lymphoma (FL), marginal zone lymphoma (MZL), splenic marginal zone lymphoma (SMZL), and DLBCL, compared to the other members of the IAP family proteins [228, 229].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [229]
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- Authors
- Rosebeck, S., Rehman, A. O., Apel, I. J., Kohrt, D., Appert, A., O'Donnell, M. A., Ting, A. T., Du, M.-Q., Baens, M., Lucas, P. C., & McAllister-Lucas, L. M.
- Affiliations
- University of Michigan (US)
- University of Cambridge (GB)
- Icahn School of Medicine at Mount Sinai (US)
- Vlaams Instituut voor Biotechnologie (BE)
- Corresponding author
- Lucas, P C
- Venue
- Oncogene
- Published
- 2013-06-17
- Volume
- 33
- Issue
- 19
- Pages
- 2520-2530
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC4237018
- OpenAlex
- W1996738870
- Cited by
- 27
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 3 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 1
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- University of Michigan Comprehensive Cancer Center
- National Heart, Lung, and Blood Institute (R01HL082914, T32-HL007622-21A2, T32HL007622)
- National Cancer Institute (R01CA124540)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- MALT lymphoma, NF-κB signaling, TRAF2, 18)(q21, oncogenic transformation, gain-of-function, lymphomagenesis
- MeSH terms
- Humans, Oncogenes, Transfection, Blotting, Western, Signal Transduction, Oncogene Proteins, Fusion, NF-kappa B, RNA-Binding Proteins, Lymphoma, B-Cell, Marginal Zone, Nuclear Pore Complex Proteins, Cell Line, Tumor, Immunoprecipitation, TNF Receptor-Associated Factor 2, Ubiquitination, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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