Mothers against decapentaplegic homolog 6

Definition:

Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators. SMAD6 is an inhibitory Smad (i-Smad) that negatively regulates signaling downstream of type I transforming growth factor-beta. Acts as a mediator of TGF-beta and BMP anti-inflammatory activities. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of pro-inflammatory genes. Blocks the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.

References:

[1]. J Massagué, et al. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91. [Content Brief]

[2]. J L Wrana, et al. The Smad pathway. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):5-13. [Content Brief]

[3]. K Miyazono, et al. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):15-22. [Content Brief]

[4]. A Hata, et al. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 1998 Jan 15;12(2):186-97. [Content Brief]

[5]. Huay L Tan, et al. Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation. Hum Mutat. 2012 Apr;33(4):720-7. [Content Brief]

[6]. D Glesne, et al. Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. Oncogene. 2006 Jul 6;25(29):4086-98. [Content Brief]

[7]. Jong Eun Park, et al. A novel SMAD6 variant in a patient with severely calcified bicuspid aortic valve and thoracic aortic aneurysm. Mol Genet Genomic Med. 2019 May;7(5):e620. [Content Brief]

[8]. K Verschueren, et al. Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells. Cytokine Growth Factor Rev. 1999 Sep-Dec;10(3-4):187-99. [Content Brief]

[9]. Kyung-Chul Choi, et al. Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1. Nat Immunol. 2006 Oct;7(10):1057-65. [Content Brief]

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