Overexpression of the inhibitory Smad, Smad7, is used frequently to implicate the Smad pathway in cellular responses to transforming growth factor beta (TGF-beta) signaling; however, Smad7 regulates several other proteins, including Cdc42, p38MAPK, and beta-catenin. We report an alternative approach for more specifically disrupting Smad-dependent signaling using a peptide aptamer, Trx-SARA, whi...

Smad proteins mediate transforming growth factor beta signaling from the cell membrane to the nucleus. Upon phosphorylation by the activated receptor kinases, the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4. This heterocomplex is then translocated into the nucleus, where it associates with other transcription factors and regulates expression of...

Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower levels of genomic DNA methylation, high express...

Mutations in SMAD tumor suppressor genes are involved in approximately 140,000 new cancers in the USA each year. At this time, how the absence of a functional SMAD protein leads to a tumor is unknown. However, clinical and biochemical studies suggest that all SMAD mutations are loss-of-function mutations. One prediction of this hypothesis is that all SMAD mutations cause tumors via a single mec...

TGF-beta can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and by means of Smad-independent mechanisms, which have been implicated in tumor progression. Although Smad mutations disable this tumor-suppressive pathway in certain cancers, breast cancer cells frequently evade the cytostatic action of TGF-beta while retaini...

The epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ-SMAD signaling pathway is an inductor of EMT in many tumor types. One hallmark of EMT is downregulation of the adherens junction protein E-cadherin, a process mediated by transcription factors such as the zinc fingers SNAIL and SLUG. Here, we report that the catalytic IκB kinase (IKK) subunit IKK...

Cell fate in multicellular organism is regulated by the diffusible factor from surrounding cells in concentration-dependent manner. TGF-beta is a large protein family of the diffusible proteins secreted from a localized source. The signal of TGF-beta is transduced by Smad family transcription factor. Though it is well known that the stoichiometry of Smads in the transcriptional complex regulate...

The SMAD (small mother against decapentaplegic) family comprises transcription factors that function as signal transducers of TGFbeta (transforming growth factor) superfamily members. The number of studies showing expression, activation or involvement of both SMAD and TGFbeta family members in cardiovascular diseases is constantly rising. In this context, the position of SMADs in the diseased h...

Introduction: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties bone marrow CD146+ mesenchymal stem cells (MSCs) and CD144+ endothelial (ECs) were separately investigated rats with POI. Methods: POI classified into control POI, + MSCs, ECs groups. Enriched MSCs directly injected tissue (15 × 104 cells/10 μL) rele...

Introduction: The aim of this study was to compare the protective effects of two types of aerobic and intermittent training on breast cancer as a result of TGFβ protein, Smad-3, and MMP2 gene in female mice. Methods: In the experimental study, a total of 24 female BALB/c mice after Tumorigenesis by MC4-L2 cell line in the three groups; Control, Aerobic, and Intermittent training groups,...