SMAD1


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SMAD1

A gene on chromosome 4q31.21 that encodes a SMAD family protein, named for their similarity to the Drosophila gene Mothers Against Decapentaplegic (Mad), which are signal transducers and transcription modulators of multiple signalling pathways. SMAD1 mediates signals from bone morphogenetic proteins (BMPs), which mediate an array of biological activities, including cell growth, apoptosis, morphogenesis, development and immune responses. In response to the binding of BMP ligands, SMAD is phosphorylated and activated by the BMP receptor kinase; phosphorylated SMAD1 forms a complex with SMAD4, resulting in transcription regulation. SMAD1 is a target for SMAD-specific E3 ubiquitin ligases—SMURF1 and SMURF2. Its activity is downregulated by ubiquitination and proteasome-mediated degradation.
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References in periodicals archive ?
To verify whether SMAD1 is the target of microRNA-205, we constructed a luciferase reporter gene of SMAD1 (pMIR-SMAD1-wild-type [WT]) and its mutation site (pMIR-SMAD1-mutanttype [MUT]) by referring to the instructions of pMIR-REPORTTM (Ambion, Grand Island, NY, USA).
The experiment showed that the molecular mechanism of osteoblast inhibition by TNF-[alpha] is via activation of NF-[kappa]B, which decreases phosphorylated Smad1 in bone morphogenetic protein 2 (BMP-2) signaling pathway (26).
Subsequent biochemical analyses found that Erk5 directly phosphorylates Smad1 at Ser206 in the linker region, which is known to trigger its proteasomal degradation in a Smad-specific E3 ubiquitin ligase 1 (Smurf1)-dependent manner.
Of interest, miR-30 family miRNAs, including miR-30b, are known in vitro negative regulators of BMP-2-induced osteogenesis, inhibiting osteoblast differentiation through targeting of Smad1 and Runx2 expression [59].
To date, eight mammalian Smad proteins have been characterized and are grouped into three functional classes: receptor-activated Smads (R-Smads) including Smad1, Smad2, Smad3, Smad5, and Smad8, common mediator Smad (Smad4), and inhibitory Smads (I-Smads) including Smad6 and Smad7.
Among the 83 TFs, six were differentially expressed: three upregulated ones, that is, zinc finger and BTB domain-containing 7A (ZBTB7A), ovo-like transcriptional repressor 1 (OVOL1), and GATA-binding protein 3, and three downregulated ones, that is, transcription factor dp-1 (TFDP1), SMAD family member 1 (SMAD1), and quiescin sulfhydryl oxidase 1 (QSOX1).
There was also an investigation that indicated loss of 4q31 (encompassing the SMAD1 gene) and loss of 18q22 as independent predictors of metastasis [5].
Besides, of the nine SMAD protein that were found, SMAD5 and SMAD1 are involved in the signal transduction of BMP (Hild et al., 2000).
(10) The BMP signal is transduced through heterotetrameric serine/ threonine kinase receptors that phosphorylate downstream pathway-restricted transcription factors Smad1, 5 and 8.
found that expression of the miR-30 family was downregulated in mouse preosteoblast differentiation and further found that miR30 targeted the important transcription factors SMAD1 and RUNX2 [9].
miR-26a expression is induced in diabetic mice wounds and its neutralization promote wound closure through increased granulation tissue, induction of SMAD1 signaling in ECs, and enhanced angiogenesis.