PDCD10 explained

Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene.^{[1] [2]}

Function

This gene encodes a protein, originally identified in a premyeloid cell line, with similarity to proteins that participate in apoptosis. Three alternative transcripts encoding the same protein, differing only in their 5' UTRs, have been identified for this gene.^[2]

Gene

Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness.^[1] Therefore, this gene is also called CCM3. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.

Interactions

CCM3 encodes a protein called Programmed Cell Death 10 (PDCD10). The function of this protein has only recently begun to be understood. PDCD10 has roles in vascular development and VEGF signaling1,^[3] apoptosis^[4] and functions as part of a larger signaling complex that includes germinal center kinase III,.^{[5] [6]} Specifically, PDCD10 has been shown to interact with RP6-213H19.1,^[7] STK25,^{[7] [8]} STRN,^[7] STRN3,^[7] MOBKL3,^[7] CTTNBP2NL,^[7] STK24^{[7] [8] [9]} and FAM40A.^[7]

Further reading

• 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 . 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 . Nov 1998 . 9811928 . 10.1093/hmg/7.12.1851 . free .
• Guclu B, Ozturk AK, Pricola KL, Seker A, Ozek M, Gunel M . Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations . Stroke: A Journal of Cerebral Circulation . 36 . 11 . 2479–80 . Nov 2005 . 16239636 . 10.1161/01.STR.0000183616.99139.d3 . free . 11424/244289 . free .
• Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M . Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3 . Neurosurgery . 57 . 5 . 1008–13 . Nov 2005 . 16284570 . 10.1227/01.NEU.0000180811.56157.E1 . 10303325 .
• Liquori CL, Berg MJ, Squitieri F, Ottenbacher M, Sorlie M, Leedom TP, Cannella M, Maglione V, Ptacek L, Johnson EW, Marchuk DA . Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus . Human Mutation . 27 . 1 . 118 . Jan 2006 . 16329096 . 10.1002/humu.9389 . 30609244 . free .
• Verlaan DJ, Roussel J, Laurent SB, Elger CE, Siegel AM, Rouleau GA . CCM3 mutations are uncommon in cerebral cavernous malformations . Neurology . 65 . 12 . 1982–3 . Dec 2005 . 16380626 . 10.1212/01.wnl.0000188903.75144.49 . 190798 .
• Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM . 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 . Sep 2006 . 16730941 . 10.1016/j.ygeno.2006.04.003 .
• Labauge P, Krivosic V, Denier C, Tournier-Lasserve E, Gaudric A . Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study . Archives of Ophthalmology . 124 . 6 . 885–6 . Jun 2006 . 16769843 . 10.1001/archopht.124.6.885 . free .
• Chen PY, Chang WS, Chou RH, Lai YK, Lin SC, Chi CY, Wu CW . 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 . 2007 . 17212813 . 1796892 . 10.1186/1471-2199-8-2 . free .
• 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 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D . 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 . Jun 2007 . 17360971 . 1877091 . 10.1091/mbc.E06-07-0608 .

External links

• www.angioma.org Angioma Alliance
• www.ccm3.org CCM3 Action

Notes and References

1. 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 . Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations . American Journal of Human Genetics . 76 . 1 . 42–51 . Jan 2005 . 15543491 . 1196432 . 10.1086/426952 .
2. Web site: Entrez Gene: PDCD10 programmed cell death 10.
3. He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W . Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development . Science Signaling . 3 . 116 . ra26 . 2010 . 20371769 . 3052863 . 10.1126/scisignal.2000722 .
4. Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M . Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3 . Neurosurgery . 57 . 5 . 1008–13 . Nov 2005 . 16284570 . 10.1227/01.NEU.0000180811.56157.E1 . 10303325 .
5. Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J . CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation . Journal of Cell Science . 123 . Pt 8 . 1274–84 . Apr 2010 . 20332113 . 10.1242/jcs.061341 . 6692474 .
6. Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F . 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 . Jul 2011 . 21561863 . 3137079 . 10.1074/jbc.M110.213777 . free .
7. 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 . 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 . Jan 2009 . 18782753 . 2621004 . 10.1074/mcp.M800266-MCP200 . free .
8. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
9. 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 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .