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.

Contents

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"

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. Type1 pcasp ig3 tree t-coffe MrBayes ugene.svg
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

Related Research Articles

<span class="mw-page-title-main">Chordate</span> Phylum of animals having a dorsal nerve cord

A chordate is a deuterostomic animal belonging to the phylum Chordata. All chordates possess, at some point during their larval or adult stages, five distinctive physical characteristics (synapomorphies) that distinguish them from other taxa. These five synapomorphies are a notochord, a hollow dorsal nerve cord, an endostyle or thyroid, pharyngeal slits, and a post-anal tail. The name "chordate" comes from the first of these synapomorphies, the notochord, which plays a significant role in chordate body plan structuring and movements. Chordates are also bilaterally symmetric, have a coelom, possess a closed circulatory system, and exhibit metameric segmentation.

<span class="mw-page-title-main">Slime mold</span> Spore-forming organisms

Slime mold or slime mould is an informal name given to a polyphyletic assemblage of unrelated eukaryotic organisms in the Stramenopiles, Rhizaria, Discoba, Amoebozoa and Holomycota clades. Most are microscopic; those in the Myxogastria form larger plasmodial slime molds visible to the naked eye. The slime mold life cycle includes a free-living single-celled stage and the formation of spores. Spores are often produced in macroscopic multicellular or multinucleate fruiting bodies that may be formed through aggregation or fusion; aggregation is driven by chemical signals called acrasins. Slime molds contribute to the decomposition of dead vegetation; some are parasitic.

<span class="mw-page-title-main">Caspase</span> Family of cysteine proteases

Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.

<span class="mw-page-title-main">Multicellular organism</span> Organism that consists of more than one cell

A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- and partially multicellular, like slime molds and social amoebae such as the genus Dictyostelium.

Programmed cell death is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's lifecycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development.

<span class="mw-page-title-main">Marine life</span> Organisms that live in salt water

Marine life, sea life, or ocean life is the plants, animals, and other organisms that live in the salt water of seas or oceans, or the brackish water of coastal estuaries. At a fundamental level, marine life affects the nature of the planet. Marine organisms, mostly microorganisms, produce oxygen and sequester carbon. Marine life, in part, shape and protect shorelines, and some marine organisms even help create new land.

<span class="mw-page-title-main">MALT lymphoma</span> Medical condition

MALT lymphoma is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zone of the MALT.

<span class="mw-page-title-main">Acrasidae</span> Family of slime moulds

The family Acrasidae is a family of slime molds which belongs to the excavate group Percolozoa. The name element acrasio- comes from the Greek akrasia, meaning "acting against one's judgement". This group consists of cellular slime molds.

Metacaspases are members of the C14 class of cysteine proteases and thus related to caspases, orthocaspases and paracaspases. The metacaspases are arginine/lysine-specific, in contrast to caspases, which are aspartate-specific.

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<span class="mw-page-title-main">Caspase 2</span> Enzyme found in humans

Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene. CASP2 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">Baculoviral IAP repeat-containing protein 3</span> Protein-coding gene in the species Homo sapiens

Baculoviral IAP repeat-containing protein3 is a protein that in humans is encoded by the BIRC3 gene.

<span class="mw-page-title-main">BCL10</span> Protein-coding gene in the species Homo sapiens

B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the BCL10 gene. Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma.

<i>Dictyostelium discoideum</i> Species of slime mould

Dictyostelium discoideum is a species of soil-dwelling amoeba belonging to the phylum Amoebozoa, infraphylum Mycetozoa. Commonly referred to as slime mold, D. discoideum is a eukaryote that transitions from a collection of unicellular amoebae into a multicellular slug and then into a fruiting body within its lifetime. Its unique asexual life cycle consists of four stages: vegetative, aggregation, migration, and culmination. The life cycle of D. discoideum is relatively short, which allows for timely viewing of all stages. The cells involved in the life cycle undergo movement, chemical signaling, and development, which are applicable to human cancer research. The simplicity of its life cycle makes D. discoideum a valuable model organism to study genetic, cellular, and biochemical processes in other organisms.

<span class="mw-page-title-main">MALT1</span> Protein-coding gene in the species Homo sapiens

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the MALT1 gene. It's the human paracaspase.

<span class="mw-page-title-main">Deuterostome</span> Superphylum of bilateral animals

Deuterostomes are bilaterian animals of the superphylum Deuterostomia, typically characterized by their anus forming before the mouth during embryonic development. Deuterostomia is further divided into 4 phyla: Chordata, Echinodermata, Hemichordata, and the extinct Vetulicolia known from Cambrian fossils. The extinct clade Cambroernida is also thought to be a member of Deuterostomia.

The evolution of nervous systems dates back to the first development of nervous systems in animals. Neurons developed as specialized electrical signaling cells in multicellular animals, adapting the mechanism of action potentials present in motile single-celled and colonial eukaryotes. Primitive systems, like those found in protists, use chemical signalling for movement and sensitivity; data suggests these were precursors to modern neural cell types and their synapses. When some animals started living a mobile lifestyle and eating larger food particles externally, they developed ciliated epithelia, contractile muscles and coordinating & sensitive neurons for it in their outer layer.

<span class="mw-page-title-main">Amoeba</span> Cellular body type

An amoeba, often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudopods. Amoebae do not form a single taxonomic group; instead, they are found in every major lineage of eukaryotic organisms. Amoeboid cells occur not only among the protozoa, but also in fungi, algae, and animals.

NHL Repeat Containing Protein 2, or NHLRC2, is a protein encoded by the NHLRC2 gene.

<span class="mw-page-title-main">CARD-CC family</span> Protein family

The CARD-CC protein family is defined by an evolutionary conserved "caspase activation and recruitment domain" (CARD) and a coiled-coil (CC) domain. Coiled-coils (CC) act as oligomerization domains for many proteins such as structural and motor proteins, and transcription factors. This means that monomers are converted to macromolecular complexes by polymerization. In humans and other jawed vertebrates, the family consists of CARD9 and the three "CARD-containing MAGUK protein" (CARMA) proteins CARD11 (CARMA1), CARD14 (CARMA2) and CARD10 (CARMA3). Although the MAGUK protein DLG5 contains both a CARD domain and a CC domain, it does not belong to the same family as the CARD-CC proteins since the evolutionary origin of its CARD domain is very likely to be different.

References

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  2. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (October 2000). "Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma". Molecular Cell. 6 (4): 961–967. doi: 10.1016/S1097-2765(05)00086-9 . PMID   11090634.
  3. 1 2 3 4 5 Hulpiau P, Driege Y, Staal J, Beyaert R (March 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. PMC   11108557 . PMID   26377317. S2CID   998306.
  4. Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (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 . PMC   5978004 . PMID   29881386.
  5. Saheb E, Biton I, Maringer K, Bush J (September 2013). "A functional connection of Dictyostelium paracaspase with the contractile vacuole and a possible partner of the vacuolar proton ATPase". Journal of Biosciences. 38 (3): 509–521. doi:10.1007/s12038-013-9338-3. PMID   23938384. S2CID   8037460.