Cited by 27NF-κB Signaling PathwaysLymphoma Diagnosis and TreatmentSignaling Pathways in Disease

The API2–MALT1 fusion exploits TNFR pathway-associated RIP1 ubiquitination to promote oncogenic NF-κB signaling

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Rosebeck, S, Rehman, A O, Apel, I J, Kohrt, D, Appert, A, O'Donnell, M A, Ting, A T, Du, M-Q +3 more·2014·Oncogene

Abstract

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].”

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  1. [47]Peng C Zhu F Wen W Yao K Li S Zykova T TRAF2 is a key mediator of the EGF-induced RSK2/CREB/Fos signaling pathway J Biol Chem 2012 6 8 PMC3406673 22685297

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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
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
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

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