Mothers against decapentaplegic homolog 7
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| Location (UCSC) | Chr 18: 48.92 – 48.95 Mb | Chr 18: 75.5 – 75.53 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.[5]
SMAD7 is a protein that, as its name describes, is a homolog of the
.Smad7 enhances muscle differentiation.
Structure
Smad proteins contain two conserved domains. The Mad Homology domain 1 (MH1 domain) is at the
Function
SMAD7 inhibits TGF-β signaling by preventing formation of Smad2/
Upon TGF- β treatment, Smad7 binds to discrete regions of Pellino-1 via distinct regions of the Smad MH2 domains. The interaction blocks the formation of the
While Smad7 is induced by TGF-β, it is also induced by other stimuli, such as
Role in cancer
A mutation located in SMAD7 gene is a cause of susceptibility to colorectal cancer (CRC) type 3.[5] Perturbation of Smad7 and suppression of TGF-β signaling was found to be evolved in CRC.[16] Case control studies and meta-analysis in Asian and European populations also provided evidence that this mutation is associated with colorectal cancer risk.[17]
TGF-β is one of the important growth factors in pancreatic cancer. By controlling the TGF-β pathway, smad7 is believed to be related to this disease. Some previous study showed over-expression of Smad7 in pancreatic cells[18][19][20] but there was a recent study showed a low Smad7 expression. The role of Smad7 in pancreatic cancer is still controversial.[21]
Over-expression or constitutive activation of
Use in Pharmacology
SMAD7 signaling has been studied in a recent Celgene Phase III trial, NCT ID number 94, which interacts with the SMAD7 pathway. This drug (Mongersen) was studied in patients with Crohn's disease.[27]
Interactions
Mothers against decapentaplegic homolog 7 has been shown to
- CTNNB1,[28]
- EP300,[29]
- TAB1,[30][31]
- PIAS4,[32]
- RNF111,[33]
- SMAD3.[34][35]
- SMAD6,[36]
- SMURF2,[37][38][39]
- STRAP,[34]
- TGFBR1,[11][33][34][37][38][40] and
- YAP1.[41]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000101665 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025880 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b EntrezGene 4092
- S2CID 4424997.
- S2CID 4421423.
- PMID 11027280.
- S2CID 25823225.
- PMID 9786930.
- ^ S2CID 16552782.
- PMID 10224135.
- S2CID 4311145.
- PMID 20171181.
- PMID 10652273.
- PMID 18781153.
- PMID 22457752.
- PMID 10498890.
- PMID 16596258.
- PMID 15150118.
- PMID 21921337.
- PMID 7612182.
- PMID 14527402.
- PMID 19385051.
- PMID 9766568.
- PMID 22033246.
- ^ "Phase II Data for Celgene's Investigational Oral GED-0301 for Patients with Active Crohn's Disease Published in New England Journal of Medicine". Celgene. Celgene Corporation. Retrieved 2015-04-20.
- PMID 15684397.
- PMID 12408818.
- PMID 12589052.
- S2CID 25476125.
- S2CID 9398438.
- ^ PMID 14657019.
- ^ PMID 10757800.
- S2CID 26825706.
- PMID 9256479.
- ^ PMID 14722617.
- ^ PMID 11163210.
- PMID 18448069.
- PMID 15148321.
- S2CID 824575.
Further reading
- Massagué J (1998). "TGF-beta signal transduction". Annu. Rev. Biochem. 67: 753–91. PMID 9759503.
- Verschueren K, Huylebroeck D (1999). "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth Factor Rev. 10 (3–4): 187–99. PMID 10647776.
- Wrana JL, Attisano L (2000). "The Smad pathway". Cytokine Growth Factor Rev. 11 (1–2): 5–13. PMID 10708948.
- Miyazono K, ten Dijke P, Heldin CH (2000). "TGF-β signaling by Smad proteins". Advances in Immunology Volume 75. Vol. 75. pp. 115–157. PMID 10879283.
- Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA, Wrana JL, Falb D (June 1997). "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling". Cell. 89 (7): 1165–73. S2CID 16552782.
- Röijer E, Morén A, ten Dijke P, Stenman G (1998). "Assignment1 of the Smad7 gene (MADH7) to human chromosome 18q21.1 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 81 (3–4): 189–90. S2CID 46753315.
- Denissova NG, Pouponnot C, Long J, He D, Liu F (June 2000). "Transforming growth factor beta -inducible independent binding of SMAD to the Smad7 promoter". Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6397–402. PMID 10823886.
- Stopa M, Anhuf D, Terstegen L, Gatsios P, Gressner AM, Dooley S (September 2000). "Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. THE TGF-beta response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation". J. Biol. Chem. 275 (38): 29308–17. PMID 10887185.
- Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K (April 2001). "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation". J. Biol. Chem. 276 (16): 12477–80. PMID 11278251.
- 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". EMBO J. 20 (15): 4132–42. PMID 11483516.