Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2–MALT1 in MALT lymphoma

Zilin Nie, Ming-Qing Du, Linda M. McAllister-Lucas, Peter C. Lucas, Nathanael G. Bailey, Cory M. Hogaboam, Megan S. Lim and Kojo S. J. Elenitoba-Johnson ()
Additional contact information
Zilin Nie: University of Michigan Medical School
Ming-Qing Du: University of Cambridge
Linda M. McAllister-Lucas: University of Pittsburgh School of Medicine
Peter C. Lucas: University of Pittsburgh School of Medicine
Nathanael G. Bailey: University of Michigan Medical School
Cory M. Hogaboam: University of Michigan Medical School
Megan S. Lim: University of Michigan Medical School
Kojo S. J. Elenitoba-Johnson: University of Michigan Medical School

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract MALT1 is the only known paracaspase and is a critical mediator of B- and T-cell receptor signalling. The function of the MALT1 gene is subverted by oncogenic chimeric fusions arising from the recurrent t(11;18)(q21;q21) aberration, which is the most frequent translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. API2–MALT1-positive MALT lymphomas manifest antibiotic resistance and aggressive clinical behaviour with poor clinical outcome. However, the mechanisms underlying API2–MALT1-induced MALT lymphomagenesis are not fully understood. Here we show that API2–MALT1 induces paracaspase-mediated cleavage of the tumour suppressor protein LIMA1. LIMA1 binding by API2–MALT1 is API2 dependent and proteolytic cleavage is dependent on MALT1 paracaspase activity. Intriguingly, API2–MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing fragment with oncogenic properties in vitro and in vivo. Importantly, primary MALT lymphomas harbouring the API2–MALT1 fusion uniquely demonstrate LIMA1 cleavage fragments. Our studies reveal a novel paracaspase-mediated oncogenic gain-of-function mechanism in the pathogenesis of MALT lymphoma.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms6908 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6908

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6908

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().