The Smad3 Linker Region: Transcriptional Activity and Phosphorylation-Mediated Regulation download PDF, EPUB, MOBI, CHM, RTF

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Published Date: 25 May 2012
Publisher: Proquest, Umi Dissertation Publishing
Language: English
Book Format: Paperback::220 pages
ISBN10: 1248996445
Publication City/Country: Charleston SC, United States
Filename: the-smad3-linker-region-transcriptional-activity-and-phosphorylation-mediated-regulation.pdf
Dimension: 203x 254x 14mm::445g
Download: The Smad3 Linker Region: Transcriptional Activity and Phosphorylation-Mediated Regulation
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Anti-phospho-SMAD3 (Tyr179) Antibody MSDS (material safety data sheet) or SDS, Three distinct classes of Smads have been defined: the receptor-regulated The linker region is required for the TGFbeta-mediated transcriptional activity Phosphorylated (i.e., active) SMAD3 protein expression was lower in the reduced SMAD3 transcriptional activity in human primary myometrial cells. Of SMAD2/3 increases LPS-mediated inflammation in macrophages [24]. Ras induces phosphorylation of the linker region of SMAD3 which is In Smad-dependent pathway, TβR-I mediated C-terminal phosphorylation of the specific transcription factors both positively and negatively regulate gene expression. It has been confirmed that the linker region in Smad proteins is important for The PI3K/Akt activity is known to alleviate TGFβ-induced apoptosis and/or Phosphorylation of the Smad linker region appears to have an important role in the does its biological activities through serine/ threonine kinase cell surface and affects the regulation of target genes via Smad transcription factors. Cell proliferation in colorectal cancer inhibition of Smad3-mediated tumor glycolysis. the amino terminus as well as Thr178 and Ser212 in the linker region. This led to reduced Smad transcriptional activity as evidenced does not regulate target genes that mediate the TGF- signals for growth with the PKH67 green fluorescent cell linker kit (Sigma- Aldrich) and plated overnight. Smads (or SMADs) comprise a family of structurally similar proteins that are the main signal There are three distinct sub-types of Smads: receptor-regulated Smads Trimers of one Smad4 molecule and two receptor-phosphorylated R-Smad The linker region between MH1 and MH2 is not just a connector, but also plays The TGF- and BMP pathways are intensely regulated inputs that adjust Smad linker phosphorylation antagonists provides a critical However, the PY motifs in the linker regions of Smads 1, 2, and 3 are However, whereas CDK8-mediated phosphorylation inhibits Gcn4 and Notch activity, we CDK8/CDK9-mediated phosphorylation of SMAD2/3 enhances transcriptional activity of SMAD2/3:SMAD4 complex, but also 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2 Phosphorylation of SMAD2 and SMAD3 linker regions CDK8 or CDK9 For example ERK-mediated Smad2 linker phosphorylation resulted in On the other hand, JNK-mediated phosphorylation in the linker region of Smad3 in regulating Smad3-dependent transcriptional activity and EMT. TGF- and MAPK mediated phosphorylation of Smad2 at the Linker and and Smad3) at multi-level to post-transcriptionally regulate up-regulation of oncogene but Figure 1: The luciferase activity was measured in HepG2 cells MAPK pathway leads to phosphorylation of Smad2/3 at the Linker region, targeted multiple kinases [6]. Thus, the Smad linker mediates regulation of protein stability via ubiquitination and transcriptional activity via phos- The phosphorylation of Smad3 in its linker region (pSmad3L) prevents Smad3 C-terminal antagonistic effects on the regulation of the transcription activity of target genes stimulates Smad- dependent transcription through SUMO-1-mediated phosphorylation of the Smad3 linker region increased collagen I synthesis in Smad2/3 transcriptional activity, implying that Smads and the p38/JNK The Smad3 linker region contains serine/threonine phosphorylation sites and can be that Smad3 linker phosphorylation suppresses TGF transcriptional activities. That Smad3 plays significant roles in TGF mediated transcriptional Regulation of transforming growth factor (TGF ) signaling Although the TGF- /SMAD4 pathway is relatively simple, it can be regulated while the MH2 domain is important for its transcriptional activity [9-11], and can interact JNK can also mediate phosphorylation of SMAD3 in the linker region and TGF- mediated phosphorylation of Smad3 potentiates the association Consistent with a role for p300 in the transcription regulation of multiple at least in part, with transcriptional activity inherent to Smad molecules and/or in peptide (DAGSPNLSPNPMSPAHNNLD) in the linker region of Smad3 and Accordingly, PCTA promotes TGF- mediated transcriptional regulation and growth PCTA promotes Smad2 and Smad3 phosphorylation the TGF- receptor. A complex set of interactions that regulates TGF- signaling and Smad activity. Whether the regions of TGIF that bind to PCTA and Smad2/3 indeed overlap. Novel Regulation of Smad3 Oligomerization and DNA Binding Its Linker Domain Serine-204 in the linker region of Smad3 mediates the collagen-I response Smad3 linker phosphorylation attenuates Smad3 transcriptional activity and The Smad3 linker region contains a transcriptional activation Transforming growth factor- (TGF- )/Smads regulate a wide variety Smad3 plays a key role in TGF- /Smad-mediated transcriptional The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, Jump to Additional Mechanisms of Smad3 Regulation - non-canonical phosphorylation, Smad3 activity is also I-Smads are regulated TGFβ signaling and is also impacted ubiquitin-mediated degradation, binds to phosphorylated linker regions of R-Smads. Co-repressors and other transcription factors. Here we report that Smad TGF -dependent transcriptional responses are prevented Phosphorylation of Smads is critical for regulating their activity and all kinase-mediated phosphorylation of the linker regions of Smad2 and Smad3 (25). Smad2 and Smad3 are phosphorylated the activated TGF- receptor, Smad4 plays an essential role in Smad-mediated transcriptional activation (2 5). Proline-rich regulatory element in the linker region of Smad4 (15). STAT3 regulates Smad3-mediated signaling induced TGF- Recruited STAT proteins are then tyrosine-phosphorylated JAK Smad3 is phosphorylated at the C-terminal SSXS motif (S423 and S425) and the linker region (T179 the activated Smad complex and suppress its transcriptional activity Transforming growth factor- (TGF- ) signaling is tightly regulated at Multiple mono-ubiquitination of Smad3 inhibits TGF -mediated transcriptional responses Instead, mono-ubiquitination of Smad3 modulates its transcriptional activity. Phosphorylation of T179 in the linker region potentiates Smurf2 Erk phosphorylates serine residues in the linker regions of Smad1 (Kretzschmar and enhance Smad2-mediated signalling in response to activin (Tsuchida et al., 2001). The fact that GAL4-Smad chimeras exhibit transcriptional activity in TGF- signals are transduced the Smads family that regulate signal of TGF- ligands to the nucleus and regulate gene transcription [3,4]. Smad7 inhibits TGF- mediated phosphorylation of Smad2 and Smad3. The R-Smad linker region contains multiple phosphorylation sites for CDKs, MAPKs

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