Characterization of a Bone Morphogenetic Protein-responsive Smad-binding Element

Kusanagi, Kiyoshi; Inoue, Hirofumi; Ishidou, Yasuhiro; Mishima, Hiromu K.; Kawabata, Masahiro; Miyazono, Kohei

doi:10.1091/mbc.11.2.555

Cited by 168 publications

(155 citation statements)

References 44 publications

(78 reference statements)

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…An important indication deduced from these observations is that the DNA binding af®nity of Smads alone may be relatively low. We found that mammalian Smad1 binds to the Mad consensus binding site found in Ubx and labial (Kusanagi et al 2000). However, the sequence speci®city for Smad1 binding was not very rigid.…”

Section: Discussionmentioning

confidence: 80%

Schnurri interacts with Mad in a Dpp‐dependent manner

et al. 2000

Self Cite

View full text Add to dashboard Cite

Background: Decapentaplegic (Dpp) is a member of the transforming growth factor-b superfamily. Dpp governs various developmental processes in Drosophila through the transcriptional regulation of a variety of genes. Signals of Dpp are transmitted from the cell membrane to the nucleus by Medea and Mad, both belonging to the Smad protein family. Mad was shown to bind to the Dpp-responsive element in genes such as vestigial, labial, and Ultrabithorax. The DNA binding af®nity of Smad proteins is relatively low, and requires other nuclear factor(s) to form stable DNA binding complexes. schnurri (shn) was identi®ed as a candidate gene acting downstream of

show abstract

Section: Discussionmentioning

confidence: 80%

Schnurri interacts with Mad in a Dpp‐dependent manner

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, Smad1 and Smad2 associate with different transcription factors, bind distinct DNA sequences and regulate distinct pools of genes. 41,44 Of course, We observed that an anti-TGFbRII Ab efficiently blocked Smad1 phosphorylation as well as the formation of Smad1/ Smad4 complexes. This supports participation of TGFbRII in the data 8).…”

Section: Tgfb-mediatedmentioning

confidence: 72%

“…Smad1/Smad4 complexes are required for DNA binding or regulation of gene transcription by Smad1. 41 Their presence further demonstrates that the phosphorylation of Smad1 observed here activates the protein, in contrast to a phosphorylation targeting its linker domain and preventing its nuclear translocation. 42 TGFb induced not only Smad1 but also Smad2 phosphorylation in H2 cells.…”

Section: Tgfb-mediatedmentioning

confidence: 73%

TGFβ-mediated activation of Smad1 in B-cell non-Hodgkin's lymphoma and effect on cell proliferation

et al. 2004

View full text Add to dashboard Cite

We have previously reported an overexpression of Smad1 in follicular lymphoma (FL) cells, which are characterized by the t(14;18) bcl2/IgH translocation. Smad1 is commonly involved in bone morphogenetic protein but not in tumor-transforming growth factor beta (TGFb) signaling pathways. This study focuses on Smad1 signaling pathway in non-Hodgkin lymphoma cells including follicular or large-cell lymphoma cells. Our results support the notion that phosphorylation of Smad1 is mediated by TGFb present in the microenvironment and occurs in FL in vivo. Using an in vitro coculture system mimicking interactions between stroma cells and FL cells, we found that both the cell partners release TGFb at a sufficient concentration to activate Smad pathways in the malignant cells. This Smad1 activation involves TGFbRII but not ALK-1 receptors, and does not compete with the Smad2 pathway. Moreover, proliferation assays performed on lymphoma cells expressing wild-type or mutated Smad1, or in which endogenous Smad1 level was decreased by gene silencing, strongly supported that overexpression and activation of Smad1 modifies the biological response of lymphoma B cells to TGFb family members. This work opens new insights into aberrant Smad pathways and their pathophysiological role in FL and in other non-Hodgkin lymphomas.

show abstract

“…Interestingly, Smad2 has 30-amino acid insertion immediately prior to the DNA-binding b-hairpin, which inhibits the capacity of Smad2 to bind to DNA (Shi et al, 1998;Dennler et al, 1999;Yagi et al, 1999). BMP RSmads (and also Smad3 and Smad4) have also been shown to bind to GC-rich sequence motifs (Kim et al, 1997;Labbe Â et al, 1998;Ishida et al, 2000;Kusanagi et al, 2000), suggesting that DNA binding speci®city of Smads is not so strict (Qing et al, 2000). GC-rich sequences have been found to be critically important for BMP-induced activation of Smad6 (Ishida et al, 2000).…”

Section: Transcriptional Control By Smadsmentioning

confidence: 99%

Regulation of cell proliferation by Smad proteins

Dijke

Goumans

Itoh

2002

Journal Cellular Physiology

398

278

View full text Add to dashboard Cite

Transforming growth factor-b (TGF-b) family members which include TGF-bs, activins, and bone morphogenetic proteins (BMPs) regulate a broad spectrum of biological responses on a large variety of cell types. TGF-b family members initiate their cellular responses by binding to distinct receptors with intrinsic serine/ threonine kinase activity and activation of speci®c downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Smad activation, subcellular distribution, and stability have been found to be intricately regulated and a broad array of transcription factors have been identi®ed as Smad partners. Important activities of TGF-b are its potent anti-mitogenic and pro-apoptotic effects that, at least in part, are mediated via Smad proteins. Escape from TGF-b/ Smad-induced growth inhibition and apoptosis is frequently observed in tumors. Certain Smads have been found to be mutated in speci®c types of cancer and gene ablation of particular Smads in mice has revealed increased rate of tumorigenesis. In late stage tumors, TGF-b has been shown to function as a tumor promoter. TGFb can stimulate the de-differentiation of epithelial cells to malignant invasive and metastatic ®broblastic cells. Interestingly, TGF-b may mediate these effects directly on tumor cells via subverted Smad-dependent and/or Smad-independent pathways.

show abstract

Characterization of a Bone Morphogenetic Protein-responsive Smad-binding Element

Cited by 168 publications

References 44 publications

Schnurri interacts with Mad in a Dpp‐dependent manner

Schnurri interacts with Mad in a Dpp‐dependent manner

TGFβ-mediated activation of Smad1 in B-cell non-Hodgkin's lymphoma and effect on cell proliferation

Regulation of cell proliferation by Smad proteins

Contact Info

Product

Resources

About