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Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions

Jens Staal (UGent) , Yasmine Driege (UGent) , Mira Haegman (UGent) , Alice Borghi (UGent) , Paco Hulpiau (UGent) , Laurens Lievens, Ismail Sahin Gül (UGent) , Srividhya Sundararaman Iyer (UGent) , Amanda Gonçalves (UGent) , Ineke Dhondt (UGent) , et al.
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Abstract
The CARD-coiled coil (CC)/Bcl10/MALT1-like paracaspase (CBM) signaling complexes composed of a CARD-CC family member (CARD-9, -10, -11, or -14), Bcl10, and the type 1 paracaspase MALT1 (PCASP1) play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians). Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects) lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD-CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD-CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein-protein interactions, NF-kappa B signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-kappa B-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1.
Keywords
NF-KAPPA-B, MULTIPLE SEQUENCE ALIGNMENT, RECEPTOR-INDUCED ACTIVATION, PROTEIN-COUPLED RECEPTOR, T-CELL, UBIQUITIN LIGASE, IKK ACTIVATION, TARGETS BCL10, MALT1, CARMA1, signal transduction, molecular evolution, protein-protein interaction, structure-function analysis NF-kappaB, coral bleaching, Nematostella, vectensis, Caenorhabditis elegans

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Chicago
Staal, Jens, Yasmine Driege, Mira Haegman, Alice Borghi, Paco Hulpiau, Laurens Lievens, Ismail Sahin Gül, et al. 2018. “Ancient Origin of the CARD-coiled coil/Bcl10/MALT1-like Paracaspase Signaling Complex Indicates Unknown Critical Functions.” Frontiers in Immunology 9.
APA
Staal, J., Driege, Y., Haegman, M., Borghi, A., Hulpiau, P., Lievens, L., Gül, I. S., et al. (2018). Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions. FRONTIERS IN IMMUNOLOGY, 9.
Vancouver
1.
Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions. FRONTIERS IN IMMUNOLOGY. 2018;9.
MLA
Staal, Jens, Yasmine Driege, Mira Haegman, et al. “Ancient Origin of the CARD-coiled coil/Bcl10/MALT1-like Paracaspase Signaling Complex Indicates Unknown Critical Functions.” FRONTIERS IN IMMUNOLOGY 9 (2018): n. pag. Print.
@article{8565443,
  abstract     = {The CARD-coiled coil (CC)/Bcl10/MALT1-like paracaspase (CBM) signaling complexes composed of a CARD-CC family member (CARD-9, -10, -11, or -14), Bcl10, and the type 1 paracaspase MALT1 (PCASP1) play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians). Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects) lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD-CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD-CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein-protein interactions, NF-kappa B signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-kappa B-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1.},
  articleno    = {1136},
  author       = {Staal, Jens and Driege, Yasmine and Haegman, Mira and Borghi, Alice and Hulpiau, Paco and Lievens, Laurens and G{\"u}l, Ismail Sahin and Sundararaman Iyer, Srividhya and Gon\c{c}alves, Amanda and Dhondt, Ineke and Pinzon, Jorge H and Braeckman, Bart and Technau, Ulrich and Saeys, Yvan and Van Roy, Frans and Beyaert, Rudi},
  issn         = {1664-3224},
  journal      = {FRONTIERS IN IMMUNOLOGY},
  language     = {eng},
  pages        = {16},
  title        = {Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.01136},
  volume       = {9},
  year         = {2018},
}

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