SMAD (protein)

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SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream gene transcription.[1][2][3][4][5][6]

The SMADs, which form a trimer of two receptor-regulated SMADs and one co-SMAD, act as transcription factors that regulate the expression of certain genes.[7][8]

Classes[edit]

There are three classes of SMAD:

  1. The receptor-regulated Smads (R-SMAD) which include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9[9]
  2. The common-mediator Smad (co-SMAD) which includes only SMAD4, which interacts with R-SMADs to participate in signaling[10]
  3. The antagonistic or inhibitory Smads (I-SMAD) which include SMAD6 and SMAD7, which block the activation of R-SMADs and Co-SMADs.[11]

Nomenclature[edit]

The SMAD proteins are homologs of both the Drosophila protein, mothers against decapentaplegic (MAD[12]) and the Caenorhabditis elegans protein SMA (from gene sma for small body size[13]). The name is a portmanteau of the two. MAD mutations can be placed in an allelic series based on the relative severity of the maternal effect enhancement of weak dpp alleles, thus explaining the name Mothers against dpp.[14]

During Drosophila research, it was found that a mutation in the gene, MAD, in the mother, repressed the gene decapentaplegic in the embryo.

Hair[edit]

Specifically, colocalization of phosphorylated Smad1/5/8 complex and DLX3 regulate role for BMP signaling to Dlx3 during hair morphogenesis in animal models.[15][16]

References[edit]

  1. ^ Heldin CH, Miyazono K, ten Dijke P (December 1997). "TGF-beta signalling from cell membrane to nucleus through SMAD proteins". Nature. 390 (6659): 465–71. PMID 9393997. doi:10.1038/37284. 
  2. ^ Attisano L, Wrana JL (April 1998). "Mads and Smads in TGF beta signalling". Current Opinion in Cell Biology. 10 (2): 188–94. PMID 9561843. doi:10.1016/S0955-0674(98)80141-5. 
  3. ^ Massagué J (1998). "TGF-beta signal transduction". Annual Review of Biochemistry. 67: 753–91. PMID 9759503. doi:10.1146/annurev.biochem.67.1.753. 
  4. ^ Attisano L, Wrana JL (May 2002). "Signal transduction by the TGF-beta superfamily". Science. 296 (5573): 1646–7. PMID 12040180. doi:10.1126/science.1071809. 
  5. ^ Whitman M (August 1998). "Smads and early developmental signaling by the TGFbeta superfamily". Genes & Development. 12 (16): 2445–62. PMID 9716398. doi:10.1101/gad.12.16.2445. 
  6. ^ Wrana JL (March 2000). "Crossing Smads". Science's STKE. 2000 (23): re1. PMID 11752591. doi:10.1126/stke.2000.23.re1. 
  7. ^ Derynck R, Zhang Y, Feng XH (December 1998). "Smads: transcriptional activators of TGF-beta responses". Cell. 95 (6): 737–40. PMID 9865691. doi:10.1016/S0092-8674(00)81696-7. 
  8. ^ Massagué J, Seoane J, Wotton D (December 2005). "Smad transcription factors". Genes & Development. 19 (23): 2783–810. PMID 16322555. doi:10.1101/gad.1350705. 
  9. ^ Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y (December 2001). "Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling". Molecular Cell. 8 (6): 1277–89. PMID 11779503. doi:10.1016/S1097-2765(01)00421-X. 
  10. ^ Shi Y, Hata A, Lo RS, Massagué J, Pavletich NP (July 1997). "A structural basis for mutational inactivation of the tumour suppressor Smad4". Nature. 388 (6637): 87–93. PMID 9214508. doi:10.1038/40431. 
  11. ^ Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". The EMBO Journal. 20 (15): 4132–42. PMC 149146Freely accessible. PMID 11483516. doi:10.1093/emboj/20.15.4132. 
  12. ^ Sekelsky JJ, Newfeld SJ, Raftery LA, Chartoff EH, Gelbart WM (March 1995). "Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster". Genetics. 139 (3): 1347–58. PMID 7768443. 
  13. ^ Savage C, Das P, Finelli AL, Townsend SR, Sun CY, Baird SE, Padgett RW (January 1996). "Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components". Proceedings of the National Academy of Sciences of the United States of America. 93 (2): 790–4. PMID 8570636. doi:10.1073/pnas.93.2.790. 
  14. ^ "Gene name - Mothers against dpp". Interactive Fly, Drosophila. Society for Developmental Biology. 
  15. ^ Hwang J, Mehrani T, Millar SE, Morasso MI (September 2008). "Dlx3 is a crucial regulator of hair follicle differentiation and cycling". Development. 135 (18): 3149–59. PMC 2707782Freely accessible. PMID 18684741. doi:10.1242/dev.022202. 
  16. ^ Park GT, Morasso MI (January 2002). "Bone morphogenetic protein-2 (BMP-2) transactivates Dlx3 through Smad1 and Smad4: alternative mode for Dlx3 induction in mouse keratinocytes". Nucleic Acids Research. 30 (2): 515–22. PMC 99823Freely accessible. PMID 11788714. doi:10.1093/nar/30.2.515. 

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