Nucleocytoplasmic shuttling of Smad proteins

Hill, Caroline S.

doi:10.1038/cr.2008.325

Cited by 212 publications

(172 citation statements)

References 52 publications

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“…Although the canonical Smad-mediated signaling is relatively simple, it is precisely controlled at different levels from the availability and activation of extracellular ligands, the activity and stability of membrane receptors to the activity, stability and localization of Smad proteins in the cytoplasm or in the nucleus (15,35,(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction

Yan

Zhang

Sun

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction

Yan

Zhang

Sun

et al. 2012

Journal of Biological Chemistry

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“…p53 (protein 53 or p53 is important in multi-cellular organisms, regulating the cell cycle and thus such functions as a tumor tumor protein 53) suppression. As such, p53 has been described as the guardian of the genome, the guardian angel gene, and the master watchman, referring to its role in conserving stability by preventing genome mutation [51].…”

Section: Nf-κbmentioning

confidence: 99%

The effects of Ankaferd Blood Stopper on transcription factors in HUVEC and erythrocyte protein profile

Yılmaz¹,

Güleç²,

Torun³

et al. 2011

Turk J Hematol

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Objective: Ankaferd ® Blood Stopper (ABS) is an herbal extract that has historically been used as a hemostatic agent in traditional Turkish medicine. ABS is comprised of a standardized herbal mixture of T. vulgaris, G. glabra, V. vinifera, A. officinarum, and U. dioica. ABS's basic mechanism of action is the formation of an encapsulated protein web, which represents the focal point for vital erythrocyte masses. The hemostatic effects of ABS have been observed in vitro and in vivo. ABS was registered as a hemostatic agent for external hemorrhages and dental bleeding following phase I randomized, double-blind crossover placebo-controlled clinical research, and safety and efficacy reports. In terms of the potential use of ABS, transcription factors may be novel factors that play a role in the hemostatic and other pleiotropic effects of ABS. Materials and Methods: Hence, the present study aimed to investigate the effects of ABS on endothelium, and possible transcription factor changes in HUVEC (human umbilical vein endothelial cells) and the erythrocyte membrane profile. ABS (5 μL and 50 μL) was administered to HUVEC (in 75 cm 2 ; ~75% fullness) for 5 min and 15 min. Results: ABS caused significant increases in the level of activation of the following transcription factors; AP2, AR, CRE/ATF1, CREB, E2F1-5, E2F6, EGR, GATA, HNF-1, ISRE, Myc-Max, NF-1, NFkB, p53, PPAR, SMAD 2/3, SP1, TRE/AP1, and YY1. Following erythrocyte membrane isolation, protein complexes were undissolved, but denatured. The protein complex formed was resistant to heat and detergent. Trypsin and sonication were used in order to break this complex; the complex dissolved and erythrocyte membrane proteins were released in SDS-PAGE. Conclusion: ABS established a very fast and solid protein web, and increased the level of transcription factor activation. Therefore the cellular effects of ABS could be related to different intracellular biological pathways. (Turk J Hematol 2011; 28: 276-85)

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“…Work over the past few years has emphasized the importance of Smads nucleocytoplasmic shuttling in TGFb signaling regulation. The duration of residence in the nucleus of Smad4 is an important event for the response to TGFb in the cells (Pierreux et al 2000, Watanabe et al 2000, Hill 2009). Many studies demonstrate that the strength and the specificity of signaling correlate with the time that Smad complexes spend in the nucleus; therefore, the activity of Smads is carefully regulated (Gurdon & Bourillot 2001, Hill 2001, ten Dijke & Hill 2004, Schmierer et al 2008.…”

Section: Discussionmentioning

confidence: 99%

A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression

D’Inzeo¹,

Nicolussi²,

Donini³

et al. 2011

Endocrine-Related Cancer

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Smad proteins are the key effectors of the transforming growth factor b (TGFb) signaling pathway in mammalian cells. Smad4 plays an important role in human physiology, and its mutations were found with high frequency in wide range of human cancer. In this study, we have functionally characterized Smad4 C324Y mutation, isolated from a nodal metastasis of papillary thyroid carcinoma. We demonstrated that the stable expression of Smad4 C324Y in FRTL-5 cells caused a significant activation of TGFb signaling, responsible for the acquisition of transformed phenotype and invasive behavior. The coexpression of Smad4 C324Y with Smad4 wild-type determined an increase of homo-oligomerization of Smad4 with receptor-regulated Smads and a lengthening of nuclear localization. FRTL-5 clones overexpressing Smad4 C324Y showed a strong reduction of response to antiproliferative action of TGFb1, acquired the ability to grow in anchorageindependent conditions, showed a fibroblast-like appearance and a strong reduction of the level of E-cadherin, one crucial event of the epithelial-mesenchymal transition process. The acquisition of a mesenchymal phenotype gave the characteristics of increased cellular motility and a significant reduction in adhesion to substrates such as fibronectin and laminin. Overall, our results demonstrate that the Smad4 C324Y mutation plays an important role in thyroid carcinogenesis and can be considered as a new prognostic and therapeutic target for thyroid cancer.

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Nucleocytoplasmic shuttling of Smad proteins

Cited by 212 publications

References 52 publications

p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction

p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction

The effects of Ankaferd Blood Stopper on transcription factors in HUVEC and erythrocyte protein profile

A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression

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