scholarly journals Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors

2021 ◽  
Vol 22 (9) ◽  
pp. 4546
Author(s):  
Shiyao Chen ◽  
Yunqi Liu ◽  
Huchen Zhou
Keyword(s):  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Regulatory System ◽  
Transforming Growth Factor Β ◽  
Molecular Signaling ◽  
Post Translational Modification ◽  
The Past ◽  
Damage Repair ◽  
Wide Range ◽  
Cancer And Inflammation

Ubiquitylation and deubiquitylation are reversible protein post-translational modification (PTM) processes involving the regulation of protein degradation under physiological conditions. Loss of balance in this regulatory system can lead to a wide range of diseases, such as cancer and inflammation. As the main members of the deubiquitinases (DUBs) family, ubiquitin-specific peptidases (USPs) are closely related to biological processes through a variety of molecular signaling pathways, including DNA damage repair, p53 and transforming growth factor-β (TGF-β) pathways. Over the past decade, increasing attention has been drawn to USPs as potential targets for the development of therapeutics across diverse therapeutic areas. In this review, we summarize the crucial roles of USPs in different signaling pathways and focus on advances in the development of USP inhibitors, as well as the methods of screening and identifying USP inhibitors.

scholarly journals The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

2002 ◽  
Vol 2 ◽  
pp. 892-925 ◽  
Author(s):  
Aaron N. Johnson ◽  
Stuart J. Newfeld
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Suppressor Activity ◽  
Wide Range ◽  
Tumor Suppressor Activity ◽  
Multicellular Organisms

Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β (TGF-β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β family. These are the molecular mechanisms utilized by TGF-β signaling pathways, the developmental roles played by TGF-β family members in a variety of species, and the growing list of cancers in which various TGF-β signaling pathways display tumor suppressor activity.

scholarly journals The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 476 ◽  
Author(s):  
Chia-Jung Li ◽  
Pei-Yi Chu ◽  
Giou-Teng Yiang ◽  
Meng-Yu Wu
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition

The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

scholarly journals Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent and Smad-Independent Signaling Pathways

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 323 ◽  
Author(s):  
Hyun Jung ◽  
Dae-Sung Lee ◽  
Seong Park ◽  
Jung Choi ◽  
Won-Kyo Jung ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Nasal Polyp ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Molecular Signaling ◽  
Tgf Β1

Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular signaling pathways involved. The production of collagen type I (Col-1) was investigated in NP tissue via immunohistochemistry and western blot analysis. NPDFs were treated with transforming growth factor (TGF)-β1 (1 ng/mL) in the presence or absence of Fx (5–30 µM). The levels of α-smooth muscle actin (α-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1), MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot analysis. The expression of Col-1 was detected in NP tissues. TGF-β1 stimulated the production of α-SMA and Col-1, and stimulated the contraction of collagen gel. However, pretreatment with Fx attenuated these effects. Furthermore, these inhibitory effects were mediated through modulation of both Smad 2/3 and Akt/SP-1 signaling pathways in TGF-β1-induced NPDFs. The results from the present study suggest that Fx may be a novel anti-fibrotic agent for the treatment of NP formation.

scholarly journals The Murine Gastrin Promoter Is Synergistically Activated by Transforming Growth Factor-β/Smad and Wnt Signaling Pathways

2004 ◽  
Vol 279 (41) ◽  
pp. 42492-42502 ◽  
Author(s):  
Shi Lei ◽  
Alexander Dubeykovskiy ◽  
Abhijit Chakladar ◽  
Lindsay Wojtukiewicz ◽  
Timothy C. Wang
Keyword(s):  
Growth Factor ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

V. TGF-β signaling pathways

2000 ◽  
Vol 279 (5) ◽  
pp. G845-G850 ◽  
Author(s):  
Rebecca G. Wells
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Matrix Effects ◽  
Matrix Deposition ◽  
Peptide Growth Factor ◽  
Wide Range ◽  
The Matrix ◽  
Extracellular Matrix Deposition ◽  
Generating Matrix

Transforming growth factor (TGF)-β is a multifunctional peptide growth factor with a wide range of potential effects on growth, differentiation, extracellular matrix deposition, and the immune response. General TGF-β signaling pathways have been described in detail over the last several years, but factors that determine the nature of the TGF-β response are poorly understood. In particular, signaling pathways that specifically mediate the matrix effects of TGF-β have received little attention, although they will be important therapeutic targets in the treatment of pathological fibrosis. This themes article focuses on TGF-β signaling and highlights potential points for generating matrix-specific responses.

Molecular signaling in pathogenesis of craniosynostosis: the role of fibroblast growth factor and transforming growth factor–β

2011 ◽  
Vol 31 (2) ◽  
pp. E7 ◽  
Author(s):  
Harvey Chim ◽  
Sunil Manjila ◽  
Alan R. Cohen ◽  
Arun K. Gosain
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cranial Sutures ◽  
Fibroblast Growth ◽  
Molecular Signaling ◽  
Ongoing Research ◽  
Suture Fusion

The interplay of signals between dura mater, suture mesenchyme, and brain is essential in determining the fate of cranial sutures and the pathogenesis of premature suture fusion leading to craniosynostosis. At the forefront of research into suture fusion is the role of fibroblast growth factor and transforming growth factor–β, which have been found to be critical in the cell-signaling cascade involved in aberrant suture fusion. In this review, the authors discuss recent and ongoing research into the role of fibroblast growth factor and transforming growth factor–β in the etiopathogenesis of craniosynostosis.

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