Advanced search
1 file | 1.91 MB

The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes

Inna Afonina (UGent) , Elien Van Nuffel (UGent) , Griet Baudelet (UGent) , Yasmine Driege (UGent) , Marja Kreike (UGent) , Jens Staal (UGent) and Rudi Beyaert (UGent)
(2016) EMBO REPORTS. 17(6). p.914-927
Author
Organization
Abstract
Mutations in CARD14 have recently been linked to psoriasis susceptibility. CARD14 is an epidermal regulator of NF-jB activation. However, the ability of CARD14 to activate other signaling pathways as well as the biochemical mechanisms that mediate and regulate its function remain to be determined. Here, we report that in addition to NF-jB signaling, CARD14 activates p38 and JNK MAP kinase pathways, all of which are dependent on the paracaspase MALT1. Mechanistically, we demonstrate that CARD14 physically interacts with paracaspase MALT1 and activates MALT1 proteolytic activity and inflammatory gene expression, which are enhanced by psoriasis-associated CARD14 mutations. Moreover, we show that MALT1 deficiency or pharmacological inhibition of MALT1 catalytic activity inhibits pathogenic mutant CARD14-induced cytokine and chemokine expression in human primary keratinocytes. Collectively, our findings demonstrate a novel role for MALT1 in CARD14-induced signaling and indicate MALT1 as a valuable therapeutic target in psoriasis.
Keywords
NF-KAPPA-B, PHARMACOLOGICAL INHIBITION, psoriasis, proteolytic activity, MALT1, inflammation, CARD14 signaling pathway, PROTEASE, CARD14, A20, ACTIVATION, INFLAMMATION, PSORIATIC SKIN, ABC-DLBCL, TERMINAL KINASE

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.91 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Afonina, Inna, Elien Van Nuffel, Griet Baudelet, Yasmine Driege, Marja Kreike, Jens Staal, and Rudi Beyaert. 2016. “The Paracaspase MALT1 Mediates CARD14-induced Signaling in Keratinocytes.” Embo Reports 17 (6): 914–927.
APA
Afonina, I., Van Nuffel, E., Baudelet, G., Driege, Y., Kreike, M., Staal, J., & Beyaert, R. (2016). The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO REPORTS, 17(6), 914–927.
Vancouver
1.
Afonina I, Van Nuffel E, Baudelet G, Driege Y, Kreike M, Staal J, et al. The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO REPORTS. 2016;17(6):914–27.
MLA
Afonina, Inna, Elien Van Nuffel, Griet Baudelet, et al. “The Paracaspase MALT1 Mediates CARD14-induced Signaling in Keratinocytes.” EMBO REPORTS 17.6 (2016): 914–927. Print.
@article{8029056,
  abstract     = {Mutations in CARD14 have recently been linked to psoriasis susceptibility. CARD14 is an epidermal regulator of NF-jB activation. However, the ability of CARD14 to activate other signaling pathways as well as the biochemical mechanisms that mediate and regulate its function remain to be determined. Here, we report that in addition to NF-jB signaling, CARD14 activates p38 and JNK MAP kinase pathways, all of which are dependent on the paracaspase MALT1. Mechanistically, we demonstrate that CARD14 physically interacts with paracaspase MALT1 and activates MALT1 proteolytic activity and inflammatory gene expression, which are enhanced by psoriasis-associated CARD14 mutations. Moreover, we show that MALT1 deficiency or pharmacological inhibition of MALT1 catalytic activity inhibits pathogenic mutant CARD14-induced cytokine and chemokine expression in human primary keratinocytes. Collectively, our findings demonstrate a novel role for MALT1 in CARD14-induced signaling and indicate MALT1 as a valuable therapeutic target in psoriasis.},
  author       = {Afonina, Inna and Van Nuffel, Elien and Baudelet, Griet and Driege, Yasmine and Kreike, Marja and Staal, Jens and Beyaert, Rudi},
  issn         = {1469-221X},
  journal      = {EMBO REPORTS},
  keyword      = {NF-KAPPA-B,PHARMACOLOGICAL INHIBITION,psoriasis,proteolytic activity,MALT1,inflammation,CARD14 signaling pathway,PROTEASE,CARD14,A20,ACTIVATION,INFLAMMATION,PSORIATIC SKIN,ABC-DLBCL,TERMINAL KINASE},
  language     = {eng},
  number       = {6},
  pages        = {914--927},
  title        = {The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes},
  url          = {http://dx.doi.org/10.15252/embr.201642109},
  volume       = {17},
  year         = {2016},
}

Altmetric
View in Altmetric
Web of Science
Times cited: