FANCF
| |
| PDB 2iqc | |
| Identificadores | |
| Símbolo | FANCF |
| Símbolos alt. | FAF, Fanconi anemia complementation group F |
| Entrez | 2188 |
| RefSeq | NP_073562.1 |
| UniProt | Q9NPI8 |
| Outros datos | |
| Locus | Cr. 11 :(22.62 – 22.63 Mb) |
FANCF (do inglés Fanconi anemia complementation group F protein, proteína do grupo de complementación F da anemia de Fanconi) é unha proteína que nos humanos están codificados polo xene FANCF do cromosoma 11.[1][2]
Interaccións
[editar | editar a fonte]FANCF presenta interaccións con FANCC,[3][4] FANCG,[3][4][5][6] FANCA[3][4][7] e FANCE.[3][8]
Función
[editar | editar a fonte]FANCF é unha proteína adaptadora que desempeña un papel clave na correcta ensamblaxe do núcleo do complexo proteico FA.[3] O núcleo do complexo FA consta de oito proteínas (FANCA, -B, -C, -E, -F, -G, -L e -M).[9][10] FANCF estabiliza a interacción entre os subcomplexos FANCC/FANCE e FANCA/FANCG e pecha o núcleo do compleco FA nunha conformación que é esencial para realizar a súa función na reparación do ADN.[3]
O núcleo do complexo FA é un complexo que se encontra no núcleo celular que é esencial para a monoubiquitinación de FANCD2 e esta forma modificada de FANCD2 colocalízase con BRCA1, RAD51 e PCNA en focos que tamén conteñen outras proteínas de reparación do ADN.[3] Todas estas proteínas funcionan xuntas para facilitar a reparación de enlaces cruzados entre as febras do ADN. Tamén funcionan noutros procesos de reparación de resposta aos danos no ADN, como a recuperación e estabilización de forcadas de replicación atascadas.[10] A proteína FoxF1 tamén interacciona coa proteína FA da parte central do complexo e induce a súa unión á cromatina para promover a reparación do ADN.[10]
Cancro
[editar | editar a fonte]Os danos no ADN parecen ser a principal causa subxacente do cancro,[11][12] e as deficiencias na expresión dos xenes de reparación do ADN parecen estar na base de moitas formas de cancro.[13][14] Se a reparación do ADN é deficiente, tenden a acumularse os danos no ADN. Ese exceso de danos no ADN pode incrementar as mutacións debido á síntese translesión tendente ao erro. O exceso de danos no ADN pode tamén incrementar as alteracións epixenéticas debido a erros durante a reparación do ADN.[15][16] Tales mutacións ou alteracións epixenéticas poden dar lugar a un cancro.
As reducións na expresión dos xenes de reparación do ADN (xeralmente causados por alteracións epixenéticas) son moi comúns nos cancros, e na maior parte dos casos son moito máis frecuentes que os defectos mutacionais en xenes de reparación do ADN en cancros.[17]
A metilación da rexión promotora do xene FANCF causa a redución da expresión da proteína FANCF.[18]
Na seguinte táboa indícanse as frecuencias da metilación do promotor de FANCF en varios tipos de cancro.
| Cancro | Frecuencia | Ref. |
|---|---|---|
| Cancro de ovario epitelial | 32% | [19] |
| Carcinoma cervical | 30% | [20] |
| Cancro de ovario | 21%-28% | [18][21] |
| Carcinomas escamosos de cabeza e pescozo | 15% | [22] |
| Cancro de pulmón de células non pequenas | 14% | [22][23] |
| Tumor de células xerminais masculinas | 6% | [24] |
En cancros de mama invasivos o microARN-210 (miR-210) está incrementado, á vez que a expresión de FANCF diminúe, e FANCF é unha das probables dianas de miR-210.[25]
Aínda que as mutacións en FANCF xeralmente non se observan en tumores humanos, viuse que un modelo de ratos deficiente en FANCF era propenso ao cancro de ovario.[26]
FANCF parece ser un dos aproximadamente 26 xenes de reparación do ADN que son reprimidos epixeneticamente en varios cancros.
Infertilidade
[editar | editar a fonte]As gónadas de ratos mutantes para FANCF funcionan anormalmente, e teñen alterado o desenvolvemento dos folículos e a espermatoxénese, como se observou noutros modelos de ratos para a anemia de Fanconi e en pacientes humanos de anemia de Fanconi.[26] O exame histolólxico dos testículos de ratos deficientes en FANCF mostrou que os túbulos seminíferos estaban desprovistos de células xerminais. Na semana 14 de idade, os ratos femias deficientes en FANCF estaban case ou compeltamente desprovistos de flículos primordiais. Concluíuse que os ratos deficientes en FANCF mostran unha depleción rápida de folículos primordiais a idades novas teñen como resultado o envellecemento do ovario.[26]
Notas
[editar | editar a fonte]- ↑ Joenje H, Oostra AB, Wijker M, di Summa FM, van Berkel CG, Rooimans MA, Ebell W, van Weel M, Pronk JC, Buchwald M, Arwert F (October 1997). "Evidence for at least eight Fanconi anemia genes". American Journal of Human Genetics 61 (4): 940–4. PMC 1715980. PMID 9382107. doi:10.1086/514881.
- ↑ "Entrez Gene: FANCF Fanconi anemia, complementation group F".
- ↑ 3,0 3,1 3,2 3,3 3,4 3,5 3,6 Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP (September 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein". The Journal of Biological Chemistry 279 (38): 39421–30. PMID 15262960. doi:10.1074/jbc.M407034200.
- ↑ 4,0 4,1 4,2 de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H (November 2000). "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG". Human Molecular Genetics 9 (18): 2665–74. PMID 11063725. doi:10.1093/hmg/9.18.2665.
- ↑ Gordon SM, Buchwald M (July 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood 102 (1): 136–41. PMID 12649160. doi:10.1182/blood-2002-11-3517.
- ↑ Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (February 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Human Molecular Genetics 10 (4): 423–9. PMID 11157805. doi:10.1093/hmg/10.4.423.
- ↑ Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics 35 (2): 165–70. PMID 12973351. doi:10.1038/ng1241.
- ↑ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (July 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal 21 (13): 3414–23. PMC 125396. PMID 12093742. doi:10.1093/emboj/cdf355.
- ↑ Kottemann MC, Smogorzewska A (January 2013). "Fanconi anaemia and the repair of Watson and Crick DNA crosslinks". Nature 493 (7432): 356–63. PMC 3700363. PMID 23325218. doi:10.1038/nature11863.
- ↑ 10,0 10,1 10,2 Pradhan A, Ustiyan V, Zhang Y, Kalin TV, Kalinichenko VV (January 2016). "Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response". Oncotarget 7 (2): 1912–26. PMC 4811506. PMID 26625197. doi:10.18632/oncotarget.6422.
- ↑ Kastan MB (April 2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Molecular Cancer Research 6 (4): 517–24. PMID 18403632. doi:10.1158/1541-7786.MCR-08-0020.
- ↑ Bernstein C, Prasad AR, Nfonsam V, Bernstein H (2013). "DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair". En Chen C. Biochemistry, Genetics and Molecular Biology. InTech,. ISBN 978-953-51-1114-6.
- ↑ Harper JW, Elledge SJ (December 2007). "The DNA damage response: ten years after". Molecular Cell 28 (5): 739–45. PMID 18082599. doi:10.1016/j.molcel.2007.11.015.
- ↑ Dietlein F, Reinhardt HC (December 2014). "Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy". Clinical Cancer Research 20 (23): 5882–7. PMID 25451105. doi:10.1158/1078-0432.CCR-14-1165.
- ↑ O'Hagan HM, Mohammad HP, Baylin SB (2008). "Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". PLoS Genetics 4 (8): e1000155. PMC 2491723. PMID 18704159. doi:10.1371/journal.pgen.1000155.
- ↑ Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV (July 2007). "DNA damage, homology-directed repair, and DNA methylation". PLoS Genetics 3 (7): e110. PMC 1913100. PMID 17616978. doi:10.1371/journal.pgen.0030110.
- ↑ Carol Bernstein and Harris Bernstein (2015). Epigenetic Reduction of DNA Repair in Progression to Cancer, Advances in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-512-209-8, InTech, Available from: http://www.intechopen.com/books/advances-in-dna-repair/epigenetic-reduction-of-dna-repair-in-progression-to-cancer
- ↑ 18,0 18,1 Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, Mok SC, D'Andrea AD (May 2003). "Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors". Nature Medicine 9 (5): 568–74. PMID 12692539. doi:10.1038/nm852.
- ↑ Ding JJ, Wang G, Shi WX, Zhou HH, Zhao EF (January 2016). "Promoter Hypermethylation of FANCF and Susceptibility and Prognosis of Epithelial Ovarian Cancer". Reproductive Sciences 23 (1): 24–30. PMID 26507869. doi:10.1177/1933719115612136.
- ↑ Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, Mansukhani M, Villella J, Meyer L, Schneider A, Gissmann L, Dürst M, Pothuri B, Murty VV (May 2004). "Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer". Cancer Research 64 (9): 2994–7. PMID 15126331. doi:10.1158/0008-5472.can-04-0245.
- ↑ Wang Z, Li M, Lu S, Zhang Y, Wang H (March 2006). "Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway". Cancer Biology & Therapy 5 (3): 256–60. PMID 16418574. doi:10.4161/cbt.5.3.2380.
- ↑ 22,0 22,1 Marsit CJ, Liu M, Nelson HH, Posner M, Suzuki M, Kelsey KT (January 2004). "Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival". Oncogene 23 (4): 1000–4. PMID 14647419. doi:10.1038/sj.onc.1207256.
- ↑ Guo M, Alumkal J, Drachova T, Gao D, Marina SS, Jen J, Herman JG (March 2015). "CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer". Discovery Medicine 19 (104): 151–8. PMID 25828518.
- ↑ Koul S, McKiernan JM, Narayan G, Houldsworth J, Bacik J, Dobrzynski DL, Assaad AM, Mansukhani M, Reuter VE, Bosl GJ, Chaganti RS, Murty VV (May 2004). "Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors". Molecular Cancer 3: 16. PMC 420487. PMID 15149548. doi:10.1186/1476-4598-3-16.
- ↑ Volinia S, Galasso M, Sana ME, Wise TF, Palatini J, Huebner K, Croce CM (February 2012). "Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA". Proceedings of the National Academy of Sciences of the United States of America 109 (8): 3024–9. PMC 3286983. PMID 22315424. doi:10.1073/pnas.1200010109.
- ↑ 26,0 26,1 26,2 Bakker ST, van de Vrugt HJ, Visser JA, Delzenne-Goette E, van der Wal A, Berns MA, van de Ven M, Oostra AB, de Vries S, Kramer P, Arwert F, van der Valk M, de Winter JP, te Riele H (January 2012). "Fancf-deficient mice are prone to develop ovarian tumours". The Journal of Pathology 226 (1): 28–39. PMID 21915857. doi:10.1002/path.2992.
Véxase tamén
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3.
- de Winter JP, Rooimans MA, van Der Weel L, van Berkel CG, Alon N, Bosnoyan-Collins L, de Groot J, Zhi Y, Waisfisz Q, Pronk JC, Arwert F, Mathew CG, Scheper RJ, Hoatlin ME, Buchwald M, Joenje H (January 2000). "The Fanconi anaemia gene FANCF encodes a novel protein with homology to ROM". Nature Genetics 24 (1): 15–6. PMID 10615118. doi:10.1038/71626.
- de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H (November 2000). "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG". Human Molecular Genetics 9 (18): 2665–74. PMID 11063725. doi:10.1093/hmg/9.18.2665.
- Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (February 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Human Molecular Genetics 10 (4): 423–9. PMID 11157805. doi:10.1093/hmg/10.4.423.
- Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (July 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal 21 (13): 3414–23. PMC 125396. PMID 12093742. doi:10.1093/emboj/cdf355.
- Taniguchi T, D'Andrea AD (October 2002). "The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC". Blood 100 (7): 2457–62. PMID 12239156. doi:10.1182/blood-2002-03-0860.
- Gordon SM, Buchwald M (July 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood 102 (1): 136–41. PMID 12649160. doi:10.1182/blood-2002-11-3517.
- Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W (May 2003). "A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome". Molecular and Cellular Biology 23 (10): 3417–26. PMC 164758. PMID 12724401. doi:10.1128/MCB.23.10.3417-3426.2003.
- Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics 35 (2): 165–70. PMID 12973351. doi:10.1038/ng1241.
- Marsit CJ, Liu M, Nelson HH, Posner M, Suzuki M, Kelsey KT (January 2004). "Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival". Oncogene 23 (4): 1000–4. PMID 14647419. doi:10.1038/sj.onc.1207256.
- Tsutsumi S, Kamata N, Vokes TJ, Maruoka Y, Nakakuki K, Enomoto S, Omura K, Amagasa T, Nagayama M, Saito-Ohara F, Inazawa J, Moritani M, Yamaoka T, Inoue H, Itakura M (June 2004). "The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD)". American Journal of Human Genetics 74 (6): 1255–61. PMC 1182089. PMID 15124103. doi:10.1086/421527.
- Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, Mansukhani M, Villella J, Meyer L, Schneider A, Gissmann L, Dürst M, Pothuri B, Murty VV (May 2004). "Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer". Cancer Research 64 (9): 2994–7. PMID 15126331. doi:10.1158/0008-5472.CAN-04-0245.
- Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP (September 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein". The Journal of Biological Chemistry 279 (38): 39421–30. PMID 15262960. doi:10.1074/jbc.M407034200.
- Meetei AR, Levitus M, Xue Y, Medhurst AL, Zwaan M, Ling C, Rooimans MA, Bier P, Hoatlin M, Pals G, de Winter JP, Wang W, Joenje H (November 2004). "X-linked inheritance of Fanconi anemia complementation group B". Nature Genetics 36 (11): 1219–24. PMID 15502827. doi:10.1038/ng1458.
- Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W (September 2005). "A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M". Nature Genetics 37 (9): 958–63. PMC 2704909. PMID 16116422. doi:10.1038/ng1626.
