Smoothened

Smoothened

Smoothened es una proteína del tipo receptor acoplado a proteínas G.[1] codificado por el gen SMO de la ruta de señalización Hedgehog, una ruta conservada de Drosophila melanogaster a humanos. Es la diana molecular del teratógeno ciclopamina.[2]

La localización celular juega un papel esencial en la función del SMO. La estimulación del receptor PTCH1 (patched) por el ligando de sonic hedgehog conduce a la traslocación del SMO al cilio primario . Además, cuando SMO está mutado en el dominio que se precisa para la localización ciliar, no puede contribuir a la activación de la ruta.[3] También se ha comprobado que SMO se une a la proteína del motor molecular de kinesina Costal-2, desempeñando un papel en la localización de la proteína Ci ( complejo Cubitus interruptus factor de transcripción).[4]

SMO puede funcionar como un oncogén. Las mutaciones que activan a SMO pueden conducir a una activación desregulada de la ruta hedgehog y al cáncer.[5]

Vista global de las rutas de transducción de señal implicadas en la apoptosis.

Contenido

Véase también

Referencias

  1. ↑ Ruiz-Gómez A, Molnar C, Holguín H, Mayor F, de Celis JF (2007). «The cell biology of Smo signalling and its relationships with GPCRs». Biochim. Biophys. Acta 1768 (4):  pp. 901–12. doi:10.1016/j.bbamem.2006.09.020. PMID 17094938. 
  2. ↑ Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA (2000). «Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine». Nature 406 (6799):  pp. 1005–9. doi:10.1038/35023008. PMID 10984056. 
  3. ↑ Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF (2005). «Vertebrate Smoothened functions at the primary cilium». Nature 437 (7061):  pp. 1018–21. doi:10.1038/nature04117. PMID 16136078. 
  4. ↑ Lum L, Zhang C, Oh S, Mann RK, von Kessler DP, Taipale J, Weis-Garcia F, Gong R, Wang B, Beachy PA (November 2003). «Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2». Mol. Cell 12 (5):  pp. 1261–74. doi:10.1016/S1097-2765(03)00426-X. PMID 14636583. 
  5. ↑ Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH, de Sauvage FJ (1998). «Activating Smoothened mutations in sporadic basal-cell carcinoma». Nature 391 (6662):  pp. 90–2. doi:10.1038/34201. PMID 9422511. 

Bibliografía

  • Chen Y, Struhl G (1996). «Dual roles for patched in sequestering and transducing Hedgehog.». Cell 87 (3):  pp. 553–63. doi:10.1016/S0092-8674(00)81374-4. PMID 8898207. 
  • Stone DM, Hynes M, Armanini M, et al. (1996). «The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.». Nature 384 (6605):  pp. 129–34. doi:10.1038/384129a0. PMID 8906787. 
  • Xie J, Murone M, Luoh SM, et al. (1998). «Activating Smoothened mutations in sporadic basal-cell carcinoma.». Nature 391 (6662):  pp. 90–2. doi:10.1038/34201. PMID 9422511. 
  • Reifenberger J, Wolter M, Weber RG, et al. (1998). «Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.». Cancer Res. 58 (9):  pp. 1798–803. PMID 9581815. 
  • Sublett JE, Entrekin RE, Look AT, Reardon DA (1999). «Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by fluorescence in situ hybridization and radiation hybrid mapping.». Genomics 50 (1):  pp. 112–4. doi:10.1006/geno.1998.5227. PMID 9628830. 
  • McGarvey TW, Maruta Y, Tomaszewski JE, et al. (1998). «PTCH gene mutations in invasive transitional cell carcinoma of the bladder.». Oncogene 17 (9):  pp. 1167–72. doi:10.1038/sj.onc.1202045. PMID 9764827. 
  • Chidambaram A, Gerrard B, Hanson M, Dean M (1998). «Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene.». Genomics 53 (3):  pp. 416–7. doi:10.1006/geno.1998.5531. PMID 9799615. 
  • Carpenter D, Stone DM, Brush J, et al. (1998). «Characterization of two patched receptors for the vertebrate hedgehog protein family.». Proc. Natl. Acad. Sci. U.S.A. 95 (23):  pp. 13630–4. doi:10.1073/pnas.95.23.13630. PMID 9811851. 
  • Detmer K, Walker AN, Jenkins TM, et al. (2000). «Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling.». Blood Cells Mol. Dis. 26 (4):  pp. 360–72. doi:10.1006/bcmd.2000.0318. PMID 11042037. 
  • Long F, Zhang XM, Karp S, et al. (2002). «Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation.». Development 128 (24):  pp. 5099–108. PMID 11748145. 
  • Incardona JP, Gruenberg J, Roelink H (2002). «Sonic hedgehog induces the segregation of patched and smoothened in endosomes.». Curr. Biol. 12 (12):  pp. 983–95. doi:10.1016/S0960-9822(02)00895-3. PMID 12123571. 
  • Lowrey JA, Stewart GA, Lindey S, et al. (2002). «Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes.». J. Immunol. 169 (4):  pp. 1869–75. PMID 12165511. 
  • Taipale J, Cooper MK, Maiti T, Beachy PA (2002). «Patched acts catalytically to suppress the activity of Smoothened.». Nature 418 (6900):  pp. 892–7. doi:10.1038/nature00989. PMID 12192414. 
  • Katayam M, Yoshida K, Ishimori H, et al. (2003). «Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy.». J. Neurooncol. 59 (2):  pp. 107–15. doi:10.1023/A:1019660421216. PMID 12241103. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). «Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.». Proc. Natl. Acad. Sci. U.S.A. 99 (26):  pp. 16899–903. doi:10.1073/pnas.242603899. PMID 12477932. 
  • Couvé-Privat S, Bouadjar B, Avril MF, et al. (2003). «Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients.». Cancer Res. 62 (24):  pp. 7186–9. PMID 12499255. 
  • Scherer SW, Cheung J, MacDonald JR, et al. (2003). «Human chromosome 7: DNA sequence and biology.». Science 300 (5620):  pp. 767–72. doi:10.1126/science.1083423. PMID 12690205. 
  • Grachtchouk V, Grachtchouk M, Lowe L, et al. (2003). «The magnitude of hedgehog signaling activity defines skin tumor phenotype.». Embo J. 22 (11):  pp. 2741–51. doi:10.1093/emboj/cdg271. PMID 12773389. 
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). «The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).». Genome Res. 14 (10B):  pp. 2121–7. doi:10.1101/gr.2596504. PMID 15489334. 
  • Chen W, Ren XR, Nelson CD, et al. (2005). «Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.». Science 306 número= 5705:  pp. 2257–60. doi:10.1126/science.1104135. PMID 15618519. 


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