cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas

Shimin Hu; Ming Qing Du; Sun Mi Park; Allison Alcivar; Like Qu; Sanjeev Gupta; Jun Tang; Mathijs Baens; Hongtao Ye; Tae H. Lee; Peter Marynen; James L. Riley; Xiaolu Yang

doi:10.1172/JCI25641

cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas

Shimin Hu, Ming Qing Du, Sun Mi Park, Allison Alcivar, Like Qu, Sanjeev Gupta, Jun Tang, Mathijs Baens, Hongtao Ye, Tae H. Lee, Peter Marynen, James L. Riley, Xiaolu Yang

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-κB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

Original language	English (US)
Pages (from-to)	174-181
Number of pages	8
Journal	Journal of Clinical Investigation
Volume	116
Issue number	1
DOIs	https://doi.org/10.1172/JCI25641
State	Published - Jan 2006
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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title = "cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas",

abstract = "The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-κB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.",

author = "Shimin Hu and Du, {Ming Qing} and Park, {Sun Mi} and Allison Alcivar and Like Qu and Sanjeev Gupta and Jun Tang and Mathijs Baens and Hongtao Ye and Lee, {Tae H.} and Peter Marynen and Riley, {James L.} and Xiaolu Yang",

year = "2006",

month = jan,

doi = "10.1172/JCI25641",

language = "English (US)",

volume = "116",

pages = "174--181",

journal = "Journal of Clinical Investigation",

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T1 - cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas

AU - Hu, Shimin

AU - Du, Ming Qing

AU - Park, Sun Mi

AU - Alcivar, Allison

AU - Qu, Like

AU - Gupta, Sanjeev

AU - Tang, Jun

AU - Baens, Mathijs

AU - Ye, Hongtao

AU - Lee, Tae H.

AU - Marynen, Peter

AU - Riley, James L.

AU - Yang, Xiaolu

PY - 2006/1

Y1 - 2006/1

N2 - The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-κB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

AB - The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-κB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

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cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas

Abstract

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