CENPA
| |
CENPA
| |
| Identificadores | |
| Símbolo | CENPA |
| Símbolos alt. | CENP-A, CenH3, proteína do centrómero A |
| Entrez | 1058 |
| PDB | [http://www.rcsb.org/pdb/explore/explore.do?pdbId=3AN2 PDB 3AN2, PDB 3NQJ, PDB 3NQU, PDB 3R45, PDB 3WTP, PDB 5CVD PDB 3AN2, PDB 3NQJ, PDB 3NQU, PDB 3R45, PDB 3WTP, PDB 5CVD] |
| RefSeq | [http://genome.ucsc.edu/cgi-bin/hgTracks?Submit=Submit&position=NP_001035891.1
NP_001800.1&rn=1 NP_001035891.1 NP_001800.1] |
| UniProt | P49450 |
| Outros datos | |
| Locus | Cr. 2 :(26.76 – 26.8 Mb) |
A proteína do centrómero A, abreviada como CENPA (tamén CENP-A), é unha proteína que nos humanos está codificada no xene CENPA do cromosoma 2.[1]
Función
[editar | editar a fonte]Os centrómeros son os dominios cromosómicos que especifican o comportamento mitótico dos cromosomas. O xene CENPA codifica unha proteína centromérica que contén un dominio con pregamento de histona relacionada coa histona H3, que é necesaria para unirse ao centrómero. A CENPA proponse que é un compoñente dun nucleosoma modificado ou estrutura similar a un nucleosoma na cal substitúe unha ou dúas copias da histona H3 convencional no núcleo tetramérico (H3-H4)2 da partícula do nucleosoma. O empalme alternativo ten como resultado a formación de múltiples variantes de transcrición que codifican distintas isoformas.[1]
Nos eucariotas superiores o recrutamento de nucleosomas CENPA nos centrómeros existentes é un proceso epixenético, independente da secuencia de ADN subxacente. En Schizosaccharomyces pombe, o recrutamento de novo de CENPA no centrómero crese que está controlado pola heterocromatina "centromérica" que rodea o centrómero, e polo mecanismo da interferencia de ARN (RNAi). Por este mecanismo fórmase ARN interferente pequeno; este forma complexos coa proteína Chp1, que despois se une á heterocromatina centromérica. Isto contribúe a recrutar outras proteínas, o que finalmente resulta nun complexo proteico que forma cohesina entre dúas cromátides irmás na cromatina centromérica. Pénsase que esta cohesina é esencial para substituír a H3 do centrómero por CENPA. A CENPA é un dos cambios epixenéticos que se cre distinguen o ADN centromérico doutros ADNs.[2] Unha vez que se engadiu CENPA, o centrómero faise autopropagante, e o mecanismo de RNAi/heterocromatina que o rodea xa non é necesario.[3]
Notas
[editar | editar a fonte]- ↑ 1,0 1,1 EntrezGene 1058
- ↑ Chueh AC, Wong LH, Wong N, Choo KH (xaneiro de 2005). "Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere". Hum. Mol. Genet. 14 (1): 85–93. PMID 15537667. doi:10.1093/hmg/ddi008.
- ↑ Folco HD, Pidoux AL, Urano T, Allshire RC (xaneiro de 2008). "Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres". Science 319 (5859): 94–7. PMC 2586718. PMID 18174443. doi:10.1126/science.1150944.
Véxase tamén
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Palmer DK, O'Day K, Trong HL, Charbonneau H, Margolis RL (1991). "Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone.". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3734–8. PMC 51527. PMID 2023923. doi:10.1073/pnas.88.9.3734.
- Sullivan KF, Hechenberger M, Masri K (1994). "Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere.". J. Cell Biol. 127 (3): 581–92. PMC 2120219. PMID 7962047. doi:10.1083/jcb.127.3.581.
- Shelby RD, Vafa O, Sullivan KF (1997). "Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites.". J. Cell Biol. 136 (3): 501–13. PMC 2134286. PMID 9024683. doi:10.1083/jcb.136.3.501.
- Valdivia MM, Figueroa J, Iglesias C, Ortíz M (1998). "A novel centromere monospecific serum to a human autoepitope on the histone H3-like protein CENP-A.". FEBS Lett. 422 (1): 5–9. PMID 9475158. doi:10.1016/S0014-5793(97)01583-4.
- Fowler KJ, Newson AJ, MacDonald AC, Kalitsis P, Lyu MS, Kozak CA, Choo KH (1998). "Chromosomal localization of mouse Cenpa gene.". Cytogenet. Cell Genet. 79 (3–4): 298–301. PMID 9605877. doi:10.1159/000134748.
- Muro Y, Azuma N, Onouchi H, Kunimatsu M, Tomita Y, Sasaki M, Sugimoto K (2000). "Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3". Clin. Exp. Immunol. 120 (1): 218–23. PMC 1905620. PMID 10759786. doi:10.1046/j.1365-2249.2000.01189.x.
- Lomonte P, Sullivan KF, Everett RD (2001). "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0". J. Biol. Chem. 276 (8): 5829–35. PMID 11053442. doi:10.1074/jbc.M008547200.
- Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH (2001). "Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype". Curr. Biol. 10 (21): 1319–28. PMID 11084331. doi:10.1016/S0960-9822(00)00769-7.
- Zeitlin SG, Shelby RD, Sullivan KF (2002). "CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis". J. Cell Biol. 155 (7): 1147–57. PMC 2199334. PMID 11756469. doi:10.1083/jcb.200108125.
- Ando S, Yang H, Nozaki N, Okazaki T, Yoda K (2002). "CENP-A, -B, and -C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells". Mol. Cell. Biol. 22 (7): 2229–41. PMC 133672. PMID 11884609. doi:10.1128/MCB.22.7.2229-2241.2002.
- Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH (2002). "Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated". J. Biol. Chem. 277 (30): 26921–6. PMID 12011073. doi:10.1074/jbc.M200620200.
- Figueroa J, Pendón C, Valdivia MM (2003). "Molecular cloning and sequence analysis of hamster CENP-A cDNA". BMC Genomics 3: 11. PMC 113255. PMID 12019018. doi:10.1186/1471-2164-3-11.
- Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH (2003). "Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc". Hum. Mol. Genet. 11 (19): 2319–29. PMID 12217960. doi:10.1093/hmg/11.19.2319.
- Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, Yoda K, Nomura F (2003). "Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer". Cancer Res. 63 (13): 3511–6. PMID 12839935.
- Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, Hatakeyama K, Ushio Y, Saya H, Hirota T (2004). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function". Dev. Cell 5 (6): 853–64. PMID 14667408. doi:10.1016/S1534-5807(03)00364-2.
- Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes Cells 9 (2): 105–20. PMID 15009096. doi:10.1111/j.1365-2443.2004.00705.x.
- Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature 428 (6984): 767–71. PMID 15085137. doi:10.1038/nature02452.
- Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004). "Structural determinants for generating centromeric chromatin". Nature 430 (6999): 578–82. PMID 15282608. doi:10.1038/nature02766.
- Sullivan BA, Karpen GH (2004). "Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin". Nat. Struct. Mol. Biol. 11 (11): 1076–83. PMC 1283111. PMID 15475964. doi:10.1038/nsmb845.
- Nikolina S, Basset EA, Robers DJ, Black BE (2010). "The structure of (CENP-A?H4)2 reveals physical features that mark centromeres". Nature 467 (7313): 347–351. PMC 2946842. PMID 20739937. doi:10.1038/nature09323.
