Mild B-cell lymphocytosis in patients with a CARD11 C49Y mutation

Buchbinder, David; Stinson, Jeffrey R.; Nugent, Diane J.; Heurtier, Lucie; Suarez, Félipe; Sukumar, Gauthaman; Dalgard, Clifton L.; Masson, Cécile; Parisot, Mélanie; Zhang, Yu; Matthews, Helen; Su, Helen C.; Durandy, Anne; Fischer, Alain; Kracker, Sven; Snow, Andrew L.

doi:10.1016/j.jaci.2015.03.008

Cited by 45 publications

(46 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Four different autosomal dominant GOF germline mutations of CARD11, G116S, E127G, G123D, and C49Y, have been discovered in 4 different families (Buchbinder et al, 2015; Snow et al, 2012). Three affect the CC domain and one variant, C49Y, is located in the N-terminal CARD.…”

Section: Human Geneticsmentioning

confidence: 99%

“…Three affect the CC domain and one variant, C49Y, is located in the N-terminal CARD. The mutant proteins aggregate, colocalize with MALT1, activate IKK, increase nuclear localization of NF-κB and transcription (Buchbinder et al, 2015; Snow et al, 2012). The germline mutations in the CC and CARD domains recapitulated or were identical to the somatic DLBCL mutations (Lenz et al, 2008).…”

Section: Human Geneticsmentioning

confidence: 99%

See 1 more Smart Citation

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Zhang

Lenardo

Baltimore

2017

Cell

1,500

1,374

View full text Add to dashboard Cite

NF-κB was discovered thirty years ago as a rapidly inducible transcription factor. Since that time it has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system. Here we summarize elaborate regulatory pathways involving this transcription factor and use recent discoveries in human genetic diseases to place specific proteins within their relevant medical and biological contexts.

show abstract

Section: Human Geneticsmentioning

confidence: 99%

Section: Human Geneticsmentioning

confidence: 99%

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Zhang

Lenardo

Baltimore

2017

Cell

1,500

1,374

View full text Add to dashboard Cite

show abstract

“…Deregulation of this process results in immunodeficiency, autoimmune diseases, or neoplastic disorders. CARMA1 missense mutations were detected initially in human activated B cell-like (ABC)-diffuse large B cell lymphoma tumors (18) and more recently in B cell lymphocytosis (19)(20)(21), adult T cell leukemia/lymphoma (22), and a form of cutaneous T cell lymphoma, named Sézary syndrome (23,24). Most mutations were mapped to within exons encoding the CARD, the coiled-coil domain, and the linker region, resulting in overcoming autoinhibition and constitutive NF-κB activation.…”

mentioning

confidence: 99%

Assembly mechanism of the CARMA1–BCL10–MALT1–TRAF6 signalosome

David

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.

show abstract

“…It has been associated to gain of function (GOF) mutations in CARD11, within the coiled-coil protein domain. Buchbinder et al 31 described 3 patients with mutations in the N-terminal region of CARD11 that resulted with B cell lymphocytosis, however they had less affected antibody responses than previously described patients. Lanternier et al 32 reported five otherwise healthy individuals who presented with one episode of invasive candidiasis and were found to have pathogenic mutations in CARD9 , recommending to consider this genetic defect in patients with systemic yeast infections.…”

Section: Clinical Immunological Phenotypes Associated With Gene Mutatmentioning

confidence: 94%

Advances in clinical immunology in 2015

Chinen

Notarangelo

Shearer

2016

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immune deficiencies (PIDs) to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by mutations found in one gene, such as a specific RTEL1 mutation causing isolated NK cell deficiency, and mutations in RAB27 resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole exome sequencing to identify gene defects, and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several PIDs, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy.

show abstract

Mild B-cell lymphocytosis in patients with a CARD11 C49Y mutation

Cited by 45 publications

References 10 publications

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Assembly mechanism of the CARMA1–BCL10–MALT1–TRAF6 signalosome

Advances in clinical immunology in 2015

Contact Info

Product

Resources

About