Title: Cleavage of NIK by the API2-MALT1 Fusion Oncoprotein Leads to Noncanonical NF-kappa B Activation
Authors: Rosebeck, Shaun ×
Madden, Lisa
Jin, Xiaohong
Apel, Ingrid J
Appert, Alex
Hamoudi, Rifat A
Noels, Heidi
Sagaert, Xavier
Van Loo, Peter
Baens, Thijs
Du, Ming-Qing
Lucas, Peter C
McAllister-Lucas, Linda M #
Issue Date: Jan-2011
Publisher: American Association for the Advancement of Science
Series Title: Science vol:331 issue:6016 pages:468-472
Abstract: Proper regulation of nuclear factor kappa B (NF-kappa B) transcriptional activity is required for normal lymphocyte function, and deregulated NF-kappa B signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-kappa B-inducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-kappa B signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-kappa B pathway in B lymphoproliferative disease.
ISSN: 0036-8075
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Human Genome Laboratory
× corresponding author
# (joint) last author

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