PDCD10
Protein 10 programirane ćelijske smrti jest protein koji je kod ljudi kodiran genom PDCD10 sa hromosoma 3.[5][6]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 212 aminokiselina, а molekulska težina 24.702 Da.[7].
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MRMTMEEMKN | EAETTSMVSM | PLYAVMYPVF | NELERVNLSA | AQTLRAAFIK | ||||
| AEKENPGLTQ | DIIMKILEKK | SVEVNFTESL | LRMAADDVEE | YMIERPEPEF | ||||
| QDLNEKARAL | KQILSKIPDE | INDRVRFLQT | IKDIASAIKE | LLDTVNNVFK | ||||
| KYQYQNRRAL | EHQKKEFVKY | SKSFSDTLKT | YFKDGKAINV | FVSANRLIHQ | ||||
| TNLILQTFKT | VA |
Funkcija
urediOvaj gen kodira protein, prvobitno identifikovan u premijeloidnoj ćelijskoj liniji, sa sličnošću sa proteinima koji učestvuju u apoptozi. Za ovaj gen su identificirana tri alternativne varijante transkripta koji kodiraju isti protein, a razlikuju se samo po svojim 5' UTR-ima.[6]
Gen
urediGubitak funkcijskih mutacija u PDCD10 dovodi do pojave bolesti cerebralnih kavernoznih malformacija (CCM).[5] Stoga se ovaj gen naziva i CCM3. Cerebralne kavernozne malformacije (CCM) su vaskularne malformacije u mozgu i kičkičmenoj moždini koje se sastoje od proširenih kapilarnih žila.
Interakcije
urediCCM3 kodira protein koji se zove proteonom programirane ćelijske smrti 10 (PDCD10). Funkcija ovog proteina je tek nedavno počela da se shvata. PDCD10 ima ulogu u vaskularnom razvoju i VEGF signalizaciji 1,[8] apoptosis[9] i funkcionira kao dio većeg signalnog kompleksa koji uključuje kinazu germinalnog centra III.[10][11] Konkretno, pokazalo se da PDCD10 međureagira sa
RP6-213H19.1,[12]
STK25,[12][13]
STRN,[12]
STRN3,[12]
MOBKL3,[12]
CTTNBP2NL,[12]
STK24[12][13][14] i
FAM40A.[12]
Modelni organizmi
uredi| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Nenormalan |
| Studija recesivne letalnosti | Nenormalan |
| Plodnost | Normalan |
| Tjelesna težina | Normalan |
| Anksioznost otvorenog polja | Normalan |
| Neurološka procjena | Normalan |
| Snaga stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Normalan |
| Radiografija | Normalan |
| Tjelesna temperatura | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Normalan |
| Hematologija | Normalan |
| Leukociti periferne krvis | Normalan |
| Mikronukleus test | Normalan |
| Težina srca | Normalan |
| Histopatologija kože | Normalan |
| Histopatologija oka | Normalan |
| Salmonella infekcija | Normalan[15] |
| Citrobacter infekcija | Normalan[16] |
| Svi testovi i analze su prema[17][18] |
U proučavanju funkcije PDCD10 korišteni su modelni organizmi. Uslovna linija nokaut-miševa, tzv. Pdcd10tm1a(KOMP)Wtsi[19][20] generirana je kao dio programa IKMC — projekta mutageneze visoke propusnosti za generiranje i distribuciju modela životinjskih bolesti zainteresiranim naučnicima.[21][22][23]
Mužjaci i ženke podvrgnute su standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti delecija.[17][24] Izvršeno je 25 testova na mutant miševima i uočene su dvije značajne abnormalnosti.[17] Nijedan homozigotni mutantni embrion nije identifikovan tokom gestacije, pa stoga nijedan nije preživeo do odbijanja. Preostali testovi su izvedeni na heterozigotnim mutantnim odraslim miševima; nisu uočene dodatne značajne abnormalnosti kod ovih životinja.[17]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000114209 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027835 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E (Jan 2005). "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations". American Journal of Human Genetics. 76 (1): 42–51. doi:10.1086/426952. PMC 1196432. PMID 15543491.
- ^ a b "Entrez Gene: PDCD10 programmed cell death 10".
- ^ "UniProt, Q9BUL8" (jezik: engleski). Pristupljeno 9. 11. 2021.
- ^ He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W (2010). "Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development". Science Signaling. 3 (116): ra26. doi:10.1126/scisignal.2000722. PMC 3052863. PMID 20371769.
- ^ Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M (Nov 2005). "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3". Neurosurgery. 57 (5): 1008–13. doi:10.1227/01.NEU.0000180811.56157.E1. PMID 16284570. S2CID 10303325.
- ^ Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J (Apr 2010). "CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation". Journal of Cell Science. 123 (Pt 8): 1274–84. doi:10.1242/jcs.061341. PMID 20332113.
- ^ Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F (Jul 2011). "CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization". The Journal of Biological Chemistry. 286 (28): 25056–64. doi:10.1074/jbc.M110.213777. PMC 3137079. PMID 21561863.
- ^ a b c d e f g h Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC (Jan 2009). "A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein". Molecular & Cellular Proteomics. 8 (1): 157–71. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
- ^ a b Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- ^ "Salmonella infection data for Pdcd10". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Pdcd10". Wellcome Trust Sanger Institute.
- ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 9. 11. 2021.
- ^ "Mouse Genome Informatics".
- ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
- ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Dopunska literatura
uredi- Craig HD, Günel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, Ogilvy CS, Berg MJ, Crawford SC, Scott RM, Steichen-Gersdorf E, Sabroe R, Kennedy CT, Mettler G, Beis MJ, Fryer A, Awad IA, Lifton RP (Nov 1998). "Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27". Human Molecular Genetics. 7 (12): 1851–8. doi:10.1093/hmg/7.12.1851. PMID 9811928.
- Guclu B, Ozturk AK, Pricola KL, Seker A, Ozek M, Gunel M (Nov 2005). "Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations". Stroke: A Journal of Cerebral Circulation. 36 (11): 2479–80. doi:10.1161/01.STR.0000183616.99139.d3. PMID 16239636.
- Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M (Nov 2005). "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3". Neurosurgery. 57 (5): 1008–13. doi:10.1227/01.NEU.0000180811.56157.E1. PMID 16284570. S2CID 10303325.
- Liquori CL, Berg MJ, Squitieri F, Ottenbacher M, Sorlie M, Leedom TP, Cannella M, Maglione V, Ptacek L, Johnson EW, Marchuk DA (Jan 2006). "Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus". Human Mutation. 27 (1): 118. doi:10.1002/humu.9389. PMID 16329096. S2CID 30609244.
- Verlaan DJ, Roussel J, Laurent SB, Elger CE, Siegel AM, Rouleau GA (Dec 2005). "CCM3 mutations are uncommon in cerebral cavernous malformations". Neurology. 65 (12): 1982–3. doi:10.1212/01.wnl.0000188903.75144.49. PMID 16380626. S2CID 190798.
- Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM (Sep 2006). "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex". Genomics. 88 (3): 333–46. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.
- Labauge P, Krivosic V, Denier C, Tournier-Lasserve E, Gaudric A (Jun 2006). "Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study". Archives of Ophthalmology. 124 (6): 885–6. doi:10.1001/archopht.124.6.885. PMID 16769843.
- Chen PY, Chang WS, Chou RH, Lai YK, Lin SC, Chi CY, Wu CW (2007). "Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner". BMC Molecular Biology. 8: 2. doi:10.1186/1471-2199-8-2. PMC 1796892. PMID 17212813.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D (Jun 2007). "PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway". Molecular Biology of the Cell. 18 (6): 1965–78. doi:10.1091/mbc.E06-07-0608. PMC 1877091. PMID 17360971.