Paracaspase

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Paracaspases (human: MALT1) are members of the C14 family of cysteine proteases.[1] Paracaspases are proteins related to caspases present in animals and slime mold, in contrast to metacaspases, which are present in plants, fungi, and "protists".[2] The phylogenetic distribution is a bit confusing, since slime mold diverged earlier than the animal/fungal split.

Paracaspase has been first identified in a recurrent t(11;18)(q21;q21) chromosomal translocation associated with a subset of MALT lymphoma. This leads to a fusion oncoprotein consisting of the carboxyl terminus of MALT1 and the amino terminus of c-IAP2. Paracaspases are more similar to caspases than metacaspases are, indicating that this group of proteases diverged from caspases from a common metacaspase ancestor.

Structure and Evolution[]

Most non-metazoan paracaspases found in amoebas or bacteria are "type 2" paracaspases with only a caspase-like domain. The animal paracaspases are most likely not directly related to the amoeba paracaspase.[3] It is currently unclear whether the paracaspases (and caspases) found in eukaryotes are a result from several (at least 2) independent horizontal gene transfer events from prokaryotes or if there has been a convergent evolution of (para)caspases evolved from the metacaspases in several different organisms within the eukaryotes.

Animals[]

"Type 2"[]

The "type 2" paracaspases in animals represent the ancestral form which only consists of a caspase-like domain. This form of paracaspase can be found in ctenophora, trichoplax, sponges and cnidarians. Cnidarians also have "type 1" paracaspases.[3]

"Type 1"[]

Phylogenetic tree of type 1 paracaspases.
Species key: Hs= Human, Gg = Chicken, Xt = African clawed frog, Dr = Zebrafish, Cm = Elephant Shark, Pm = Lamprey, Bf = Lancelet, Sk = Acorn worm, Cg = Pacific oyster, Ob = Octopus, Dp = Daphnia, Am = Honey bee, Ce = nematode, Nv = Nematostella, Hv = Hydra.

The "type 1" paracaspases are characterized by a MALT1-like domain composition with a death domain, immunoglobulin-like domains and a caspase-like domain. The "type 1" paracaspases first originated sometime before the last common ancestor of the bilaterans and cnidaria, indicating that "type 1" paracaspases originated during the ediacaran period.[3] The jawed vertebrates (starting from sharks) have 3 paralogs: PCASP1, PCASP2 and PCASP3. PCASP3 is the ancestral copy and can be found in all deuterostomes, like sea urchin, lancelets, tunicates and lampreys (a non-jawed vertebrate). Notably, mammals have lost PCASP2 and PCASP3 and only have PCASP1 (MALT1).[3] The non-deuterostome invertebrate type 1 paracaspase closest related to PCASP3 can surprisingly be found in molluscs, which could indicate that there were 2 paralog type 1 paracaspases present in the first bilaterans (like in cnidarians), and that different bilateran lineages have kept one or the other paralog.[4]

Known functions[]

Amoebas[]

The paracaspase in Dictyostelium seems to regulate osmotic stress tolerance by vacuolar expansion.[5]

Animals[]

Paracaspase in animals has mostly been studied in humans and mice (see: MALT1), where it plays a major role in several pro-inflammatory pathways in innate- and adaptive- immunity. The distantly related zebrafish PCASP3 show conserved MALT1-like activity in NF-kappaB activation and protease substrate specificity, indicating that these functions were present in the last common ancestor of the three vertebrate paracaspase paralogs.[3]

See also[]

References[]

  1. ^ Minina EA, Staal J, Alvarez VE, Berges JA, Berman-Frank I, Beyaert R; et al. (2020). "Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases". Mol Cell. 77 (5): 927–929. doi:10.1016/j.molcel.2019.12.020. PMC 7325697. PMID 32142688.CS1 maint: multiple names: authors list (link)
  2. ^ Uren A, O'Rourke K, Aravind L, Pisabarro M, Seshagiri S, Koonin E, Dixit V (2000). "Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma". Mol Cell. 6 (4): 961–7. doi:10.1016/S1097-2765(05)00086-9. PMID 11090634.
  3. ^ Jump up to: a b c d e Hulpiau P, Driege Y, Staal J, Beyaert R (2016). "MALT1 is not alone after all: identification of novel paracaspases". Cellular and Molecular Life Sciences. 73 (5): 1103–1116. doi:10.1007/s00018-015-2041-9. PMID 26377317.
  4. ^ Staal, Jens; Driege, Yasmine; Haegman, Mira; Borghi, Alice; Hulpiau, Paco; Lievens, Laurens; Gul, Ismail Sahin; Sundararaman, Srividhya; Gonçalves, Amanda; Dhondt, Ineke; Pinzón, Jorge H.; Braeckman, Bart P.; Technau, Ulrich; Saeys, Yvan; van Roy, Frans; Beyaert, Rudi (2018). "Ancient Origin of the CARD–Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi:10.3389/fimmu.2018.01136. ISSN 1664-3224. PMC 5978004. PMID 29881386.
  5. ^ Saheb E, Biton I, Maringer K, Bush J (2013). "A functional connection of Dictyostelium paracaspase with the contractile vacuole and a possible partner of the vacuolar proton ATPase". J Biosci. 38 (3): 509–21. doi:10.1007/s12038-013-9338-3. PMID 23938384.
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