scholarly journals Structural biology of the TGFβ family

2019 ◽  
Vol 244 (17) ◽  
pp. 1530-1546 ◽  
Author(s):  
Erich J Goebel ◽  
Kaitlin N Hart ◽  
Jason C McCoy ◽  
Thomas B Thompson
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Structural Biology ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Biological Processes ◽  
Tgfβ Signaling ◽  
Growth Factor Beta ◽  
Tgfβ Signaling Pathway

The transforming growth factor beta (TGFβ) signaling pathway orchestrates a wide breadth of biological processes, ranging from bone development to reproduction. Given this, there has been a surge of interest from the drug development industry to modulate the pathway – at several points. This review discusses and provides additional context for several layers of the TGFβ signaling pathway from a structural biology viewpoint. The combination of structural techniques coupled with biophysical studies has provided a foundational knowledge of the molecular mechanisms governing this high impact, ubiquitous pathway, underlying many of the current therapeutic pursuits. This work seeks to consolidate TGFβ-related structural knowledge and educate other researchers of the apparent gaps that still prove elusive. We aim to highlight the importance of these structures and provide the contextual information to understand the contribution to the field, with the hope of advancing the discussion and exploration of the TGFβ signaling pathway. Impact statement The transforming growth factor beta (TGFβ) signaling pathway is a multifacetted and highly regulated pathway, forming the underpinnings of a large range of biological processes. Here, we review and consolidate the key steps in TGFβ signaling using literature rooted in structural and biophysical techniques, with a focus on molecular mechanisms and gaps in knowledge. From extracellular regulation to ligand–receptor interactions and intracellular activation cascades, we hope to provide an introductory base for understanding the TGFβ pathway as a whole.

scholarly journals Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 960 ◽  
Author(s):  
Panagiotis Papoutsoglou ◽  
Corentin Louis ◽  
Cédric Coulouarn
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Efficient Treatment ◽  
Tumor Onset ◽  
Tgfβ Signaling Pathway

Cholangiocarcinoma is a deadly cancer worldwide, associated with a poor prognosis and limited therapeutic options. Although cholangiocarcinoma accounts for less than 15% of liver primary cancer, its silent nature restricts early diagnosis and prevents efficient treatment. Therefore, it is of clinical relevance to better understand the molecular basis of cholangiocarcinoma, including the signaling pathways that contribute to tumor onset and progression. In this review, we discuss the genetic, molecular, and environmental factors that promote cholangiocarcinoma, emphasizing the role of the transforming growth factor β (TGFβ) signaling pathway in the progression of this cancer. We provide an overview of the physiological functions of TGFβ signaling in preserving liver homeostasis and describe how advanced cholangiocarcinoma benefits from the tumor-promoting effects of TGFβ. Moreover, we report the importance of noncoding RNAs as effector molecules downstream of TGFβ during cholangiocarcinoma progression, and conclude by highlighting the need for identifying novel and clinically relevant biomarkers for a better management of patients with cholangiocarcinoma.

scholarly journals Transforming growth factor beta (TGFβ) signaling is regulated at the pocket region of primary cilia

Cilia ◽  
2012 ◽  
Vol 1 (S1) ◽  
Author(s):  
S Christensen ◽  
CA Clement ◽  
SK Brorsen ◽  
KD Ajbro ◽  
M de Jesus ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Primary Cilia ◽  
Transforming Growth Factor ◽  
Tgfβ Signaling ◽  
Growth Factor Beta

scholarly journals Axolotl as a Model to Study Scarless Wound Healing in Vertebrates: Role of the Transforming Growth Factor Beta Signaling Pathway

2013 ◽  
Vol 2 (5) ◽  
pp. 250-260 ◽  
Author(s):  
Jean-François Denis ◽  
Mathieu Lévesque ◽  
Simon D. Tran ◽  
Aldo-Joseph Camarda ◽  
Stéphane Roy
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

scholarly journals Does Porcine Oocytes Maturation in Vitro is Regulated by Genes Involved in Transforming Growth Factor Beta Receptor Signaling Pathway?

2017 ◽  
Vol 5 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Joanna Budna ◽  
Piotr Celichowski ◽  
Paresto Karimi ◽  
Wiesława Kranc ◽  
Artur Bryja ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Oocyte Growth ◽  
Maturation In Vitro ◽  
Differential Expression Pattern ◽  
Before And After ◽  
Growth Factor Beta

Summary The oocyte growth and development in follicular environment are substantially accompanied by surrounding somatic cumulus (CCs) and granulosa cells (GCs). During these processes, the mammalian gametes reach full maturational stage and may be further successfully fertilized by single spermatozoon. These unique mechanisms are regulated by expression of clusters of genes and their biochemical signaling pathways. In this article we described differential expression pattern of transforming growth factor beta (TGFB) gene superfamily in porcine oocytes before and after in vitro maturation (IVM). We performed Affymetrix® microarray assays to investigate the TGFB-related genes expression profile in porcine immature oocytes and gametes cultured for 44h in vitro. In results we found 419 different genes, 379 genes with lower expression, and 40 genes characterized by increased RNA profile. Moreover, significant up-regulation of 6 genes belonging to TGFB signaling pathway such as: TGFBR3, SMAD4, FOS, KLF10, ID1, MAP3K1 in immature porcine oocytes (before IVM), was also observed. It may be suggested that genes involved in TGFB-related signaling pathway are substantially regulated before IVM. Furthermore, these genes may play a significant role during early stages of nuclear and/or cytoplasmic porcine oocytes maturation. The investigated transcripts may be also recommended as the markers of oocytes maturational capability in pigs.

scholarly journals TGFβ (Transforming Growth Factor-Beta)–Activated Kinase 1 Regulates Arteriovenous Fistula Maturation

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Haidi Hu ◽  
Shin-Rong Lee ◽  
Hualong Bai ◽  
Jianming Guo ◽  
Takuya Hashimoto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Wall Thickening ◽  
Laminar Shear Stress ◽  
Tgfβ Signaling ◽  
Luminal Diameter ◽  
Ecm Extracellular Matrix ◽  
Growth Factor Beta

Objective: Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFβ [transforming growth factor-beta]–activated kinase 1) is a mediator of noncanonical TGFβ signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation. Approach and Results: In both human and mouse AVF, immunoreactivity of TAK1, JNK (c-Jun N-terminal kinase), p38, collagen 1, and fibronectin was significantly increased compared with control veins. Manipulation of TAK1 in vivo altered AVF wall thickening and luminal diameter; reduced TAK1 function was associated with reduced thickness and smaller diameter, whereas activation of TAK1 function was associated with increased thickness and larger diameter. Arterial magnitudes of laminar shear stress (20 dyne/cm 2 ) activated noncanonical TGFβ signaling including TAK1 phosphorylation in mouse endothelial cells. Conclusions: TAK1 is increased in AVF, and TAK1 manipulation in a mouse AVF model regulates AVF thickness and diameter. Targeting noncanonical TGFβ signaling such as TAK1 might be a novel therapeutic approach to improve AVF maturation.

The Role of TGF-β Signaling Regulatory MicroRNAs in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4611-4618 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Majid Khazaei ◽  
Gordon A. Ferns ◽  
Seyed H. Aghaee-Bakhtiari
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Growth Factor Beta ◽  
And Migration ◽  
Multiple Signaling ◽  
Tgf Β1

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high mortality rate. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in normal intestinal tissue function, but has also been implicated in the development of CRC. MicroRNAs (miRNAs) have also recently emerged as important regulators of cancer development and progression. They act by targeting multiple signaling pathways including the TGF-β signaling pathway. There is growing evidence demonstrating that miRNAs target various components of the TGF-β signaling pathway, including TGF-β1, TGF-β2, regulatory SMADs (SMAD1, 2, 3, 5 and 9), co-mediator SMAD4, inhibitory SMADs (SMAD6 and 7) and the TGF-β receptors, and thereby alter the proliferation and migration of CRC cells. In this review, we summarize the data concerning the interaction between TGF-β signaling pathway and miRNAs with the aim to better understanding the CRC molecular mechanisms and hence better management of this disease.

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