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(acyl-carrier-protein) phosphodiesterase

this article is rated as a stub by wikipedia

  • everything in this article seems to be relevant for the protein "acyl-carrier-protein phosphodiesterase"
    • however there little information and structure to the article (only a few sentences about the catalyzed reaction and one subheading)
  • the article is neutral, without bias or making claims
  • each citation leads to legitimate research articles about the enzyme
    • however there are no in text citations
  • more information is needed about this protein to complete the article
    • perhaps information on the organism in which the protein is found, the physical structure of the protein, the mechanism by which it catalyzes the reaction, and the pathways/processes it is involved in

Possible Article Topics

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CED9 (gene)

(6-4)DNA photolyase

[[1]]

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added two sentences to MecA (gene) article

CED-9 (gene)

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Cell death abnormality gene 9 (CED-9), also known as apoptosis regulator CED-9, is a gene found in Caenorhabditis elegans that inhibits/represses programmed cell death (apoptosis).[1] The gene was discovered while searching for mutation in the apoptotic pathway after the discovery of the pro-apoptotic genes CED-3 and CED-4.[2] The gene gives rise to the apoptosis regulator CED-9 protein found as a Integral membrane protein in the mitochondrial membrane.[3] The protein is homologous to the human apoptotic regulator Bcl-2 as well as all other proteins in the Bcl-2 protein family.[4] CED-9 is involved in the inhibition of CED-4 which is the activator of the CED-3 caspase.

Discovery

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The CED-9 gene was discovered in 1992 while searching the genome of C. elegans for mutations affecting cell death.[2] The first mutation identified was a dominant, gain of function mutation referred to as n1950 that allowed cells to survive when they were fated to die.[2] The observed phenotype was similar to that observed in CED-3 and CED-4 loss of function mutants (known proteins from the apoptotic pathway).[2] It was also observed that loss of function mutations in CED-3 and CED-4 were able to rescue cells with a CED-9 loss of function mutation.[5] these observations suggested that CED-9 functioned upstream of these proteins in the same pathway.[5]

Structure

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Gene

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The CED-9 gene is located on chromosome 3 of the C. elegans genome.[1] CED-9 is transcribed from a polycistronic locus that also contains genes required for the mitochondrial Oxidative phosphorylation.[4] The CED-9 gene has been identified in two distinct transcripts, both from this locus.[4] The first was identified as a 1.3 kb transcript encoding only the CED-9 sequence, the second being a rare 2.1 kb bicistronic transcript containing the 1.3 kb transcript and an additional 0.75 kb transcript from an upstream gene in the locus.[4] this 0.75 kb transcript corresponds to a cytochrome protein, cyt-1, found in the transport chain within the mitochondria.[4] The bicistronic transcript is spliced giving rise to the two distinct mature messenger RNA for both genes.[4] The most prevalent transcript however, is the 1299-nucleotide long transcript that gives rise to an 843-nucleotide mRNA containing 4 exon.[6]

Protein

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CED-9 encodes the apoptosis regulator CED-9 protein which is an important negative regulator protein in the apoptosis pathway of C. elegans.[7] The protein consists of 280 amino acids and has a molecular weight of 31824.42 Da.[8] The structure of this protein has been solved using X-ray crystallography revealing a 9 Helix, 2 Beta strands, and 2 turn motifs.[3] The CED-9 protein belongs to the Bcl-2-like protein family. This refers to the homology between the ced-9 protein and the B-cell lymphoma proteins (Bcl) found in humans, specifically the Bcl-2 proteins.[4] CED-9 contains a BCL domain homologous to Bcl-2 domains BH1, BH2, and part of BH3 as well as a separate domain homologous to BH4 located near the N-terminus.[9] CED-9 also includes a transmembrane domain on the C-terminal end of the structure that anchors the protein to the mitochondrial membrane.[10] However, research has provided evidence that the C-terminal domain is not necessary for the protein's main function as an inhibitor of the CED-4 protein found in the same apoptosis signalling pathway.[10]

Function

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Cell death, or apoptosis during early development is crucial for the correct morphology and refractivity of adult C. elegans.[11] This process involves a signal and interaction cascade of proteins leading to the engulfment and death of the targeted cell. Proteins in this cascade can be categorized into two groups; pro-apoptotic and anti-apoptotic.[11] Pro-apoptotic proteins activate the apoptosis pathway while anti-apoptotic proteins suppress the pathway.[12] CED-9 is classified as an anti-apoptotic protein.[13]

Cell death in C. elegans can be simplified to interactions between four major proteins in the pathway; EGL-1, CED-9, CED-4, and CED-3. CED-3 is the final protease in the interaction network and is responsible for activating the proteins involved in cell disassembly.[11] CED-9 is said to protect cells from the apoptosis pathway.[5] Under normal conditions, in a cell not experiencing apoptotic signalling, CED-9 forms a complex with CED-4 at the membrane of the mitochondria.[12] This interaction sequesters the pro-apoptotic signalling of CED-4. CED-4 consists of an asymmetric dimer of CED-4a and CED-4b proteins in which CED-9 can specifically recognize and bind CED-4a.[12] This interaction is a highly specific recognition and binding interaction between the N-terminal tails of both proteins.[12] When the cell receives an apoptotic signal via a receptor commonly referred to as a "death receptor", the protein EGL-1 is activated.[14] The active EGL-1 binds CED-9 causing a Conformational change that interrupts and inhibits the CED-9 - CED-4 interaction.[12] CED-4 is free to dissociate and activate the CED-3 protease effectively triggering the final stages for apoptosis.[14]

Mutations

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The cells developed during embryogenesis and early life in C. elegans have one of two fates, to live and differentiate or apoptose.[15] Apoptosis during development is highly regulated and only occurs in specific cells at specific times.[15] Every cell division and cell death in the development of C. elegans from embryo to adult has been studied and documented to reveal a fixed pattern between individual organisms.[15] Apoptosis during development is important for the proper morphology and refractivity of C. elegans, but it is not essential for survival.[15] Thus, over 100 mutations have been observed and documented as affecting the apoptotic pathway of C. elegans.[5] Many proteins involved in the interaction cascade were discovered because of these mutations and their resulting phenotype. CED-9 mutants are among the mutations that affect this pathway. CED-9 gain of function mutations are unresponsive to apoptosis signalling and allow cells fated to die, to survive.[5] Loss of function mutations cause inappropriate cell death in the absence of apoptosis stimuli.[5] Mutations in CED-9 also reveal its maternal effect where the genotype of the mother determines the phenotype of the progeny.[5] Homozygous, loss of function mutants from a heterozygous mother experience some unpredictable cell death, however, give rise to unviable progeny themselves.[5]

Significance

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The apoptotic pathway has been conserved in evolutionary history and is vital for the maintenance of multicellular organisms such as humans.[16] A parallel pathway to the one found in C. elegans is also observed in mammals, involving a number of homologous proteins. Disruptions to this pathway often lead to human diseases that include various cancer, autoimmune diseases, and neurodegenerative disease.[16] Bcl-2 in particular is often found mutated in many human cancers.[17] CED-9 is the homologue of Bcl-2 and can provide researchers with information including which pathways the protein is a part of that may parallel pathways in humans.[17]

Interactions

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http://www.wormbase.org/species/c_elegans/gene/WBGene00000423?from=http://www.wormbase.org/db/gene/gene?name=WBGene00000423;class=Gene#0c-8-3

Good job. Keep it up! AdamCF87 (talk) 17:42, 5 October 2017 (UTC)

  1. ^ a b "ced-9 Apoptosis regulator ced-9 [Caenorhabditis elegans] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-11-16.
  2. ^ a b c d Hengartner, M. O.; Ellis, R. E.; Horvitz, H. R. (1992-04-09). "Caenorhabditis elegans gene ced-9 protects cells from programmed cell death". Nature. 356 (6369): 494–499. doi:10.1038/356494a0. ISSN 0028-0836. PMID 1560823. S2CID 4336417.
  3. ^ a b "ced-9 - Apoptosis regulator ced-9 - Caenorhabditis elegans - ced-9 gene & protein". www.uniprot.org. Retrieved 2017-11-16.
  4. ^ a b c d e f g Hengartner, Michael O.; Horvitz, H. Robert (1994-02-25). "C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2". Cell. 76 (4): 665–676. doi:10.1016/0092-8674(94)90506-1. PMID 7907274. S2CID 29437409.
  5. ^ a b c d e f g h Riddle, Donald L.; Blumenthal, Thomas; Meyer, Barbara J.; Priess, James R. (1997). Genetics of Programmed Cell Death. Cold Spring Harbor Laboratory Press.
  6. ^ a b c "ced-9". Wormbase.
  7. ^ "Family: BH4 (PF02180)". pfam.xfam.org. Retrieved 2017-11-16.
  8. ^ "ExPASy". web.expasy.org. Retrieved 2017-11-16.
  9. ^ "SMART: Sequence analysis results for CED9_CAEEL". smart.embl.de. Retrieved 2017-11-16.
  10. ^ a b Tan, FJ; Fire, AZ; Hill, RB (2007-11-14). "Regulation of apoptosis by C. elegans CED-9 in the absence of the C-terminal transmembrane domain". Cell Death and Differentiation. 14 (11): 1925–1935. doi:10.1038/sj.cdd.4402215. ISSN 1350-9047. PMC 3047747. PMID 17703231.
  11. ^ a b c Conradt, Barbara; Wu, Yi-Chun; Xue, Ding (2016-08-04). "Programmed Cell Death During Caenorhabditis elegans Development". Genetics. 203 (4): 1533–1562. doi:10.1534/genetics.115.186247. ISSN 0016-6731. PMC 4981262. PMID 27516615.
  12. ^ a b c d e Yan, Nieng; Chai, Jijie; Lee, Eui Seung; Gu, Lichuan; Liu, Qun; He, Jiaqing; Wu, Jia-Wei; Kokel, David; Li, Huilin (2005-10-06). "Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans". Nature. 437 (7060): 831–837. doi:10.1038/nature04002. ISSN 1476-4687. PMID 16208361. S2CID 4418637.
  13. ^ Jarpe, Matthew B; Widmann, Christian; Knall, Cindy; Schlesinger, Thomas K; Gibson, Spencer; Yujiri, Toshiaki; Fanger, Gary R; Gelfand, Erwin W; Johnson, Gary L (1998-09-17). "Anti-apoptotic versus pro-apoptotic signal transduction: Checkpoints and stop signs along the road to death". Oncogene. 17 (11): 1475–1482. doi:10.1038/sj.onc.1202183. ISSN 1476-5594. PMID 9779994. S2CID 21986272.
  14. ^ a b del Peso, L.; González, V. M.; Núñez, G. (1998-12-11). "Caenorhabditis elegans EGL-1 disrupts the interaction of CED-9 with CED-4 and promotes CED-3 activation". The Journal of Biological Chemistry. 273 (50): 33495–33500. doi:10.1074/jbc.273.50.33495. ISSN 0021-9258. PMID 9837929.
  15. ^ a b c d Hedgecock, E. M.; Sulston, J. E.; Thomson, J. N. (1983-06-17). "Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans". Science (New York, N.Y.). 220 (4603): 1277–1279. doi:10.1126/science.6857247. ISSN 0036-8075. PMID 6857247.
  16. ^ a b Rudin, C. M.; Thompson, C. B. (1997). "Apoptosis and disease: regulation and clinical relevance of programmed cell death". Annual Review of Medicine. 48: 267–281. doi:10.1146/annurev.med.48.1.267. ISSN 0066-4219. PMID 9046961.
  17. ^ a b Arvanitis, Marios; Li, De-Dong; Lee, Kiho; Mylonakis, Eleftherios (2013-10-18). "Apoptosis in C. elegans: lessons for cancer and immunity". Frontiers in Cellular and Infection Microbiology. 3: 67. doi:10.3389/fcimb.2013.00067. ISSN 2235-2988. PMC 3798828. PMID 24151577.
  18. ^ a b c Lab, Mike Tyers. "ced-9 (T07C4.8) Result Summary | BioGRID". thebiogrid.org. Retrieved 2017-11-29.
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