TGF-β signaling pathway mediated by deubiquitinating enzymes

Kim, Soo-Yeon; Baek, Kwang‐Hyun

doi:10.1007/s00018-018-2949-y

Cited by 43 publications

(27 citation statements)

References 181 publications

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“…These signaling pathways interact with each other. Upregulation of USP expression in tumor cells often suggests that its substrate protein can promote the malignant progression of cancer cells [32]. Downregulated expression of a USP suggests that its substrate is usually a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

et al. 2020

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Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitinspecific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells). Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK). Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

et al. 2020

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“…According to the present study, the two clawed frogs' bHLH genes share a common TGF-beta signaling pathway which was significantly enriched in both the frogs genomes. Previous reports have shown that the specific signal transduction by TGF-beta family in vertebrates involves many sets of polypeptide growth factors, receptor complexes of serine/threonine kinases and Smad proteins acting as receptor substrates with Smad-associated transcription factors (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019). Members of TGF-beta family include TGF-beta factors, activins, Bone Morphogenetic Proteins (BMPs) and other related growth factors that regulate cell division, differentiation, motility, adhesion and death in the metazoan organs and tissues (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that the specific signal transduction by TGF-beta family in vertebrates involves many sets of polypeptide growth factors, receptor complexes of serine/threonine kinases and Smad proteins acting as receptor substrates with Smad-associated transcription factors (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019). Members of TGF-beta family include TGF-beta factors, activins, Bone Morphogenetic Proteins (BMPs) and other related growth factors that regulate cell division, differentiation, motility, adhesion and death in the metazoan organs and tissues (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019). Because of the diverse processes controlled by different TGFbeta family members and their various roles in pathogenesis and/or tumorigenesis and development biology, there is an intense interest in studies on the compositional basis and relevant genes for the tissuespecific signal transduction pathways in vertebrates (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Members of TGF-beta family include TGF-beta factors, activins, Bone Morphogenetic Proteins (BMPs) and other related growth factors that regulate cell division, differentiation, motility, adhesion and death in the metazoan organs and tissues (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019). Because of the diverse processes controlled by different TGFbeta family members and their various roles in pathogenesis and/or tumorigenesis and development biology, there is an intense interest in studies on the compositional basis and relevant genes for the tissuespecific signal transduction pathways in vertebrates (Liu et al, 1996;Lagna et al, 1996;Derynck et al, 1996;Chen et al, 1998;Upadhyay et al, 2017;Kim and Baek, 2019). In our analysis, it has been reported that the two clawed frogs' bHLH proteins as important transcription factors were commonly involved in TGFbeta signaling pathway with significant P Values of functional enrichment.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Functional Analysis of the Basic Helix-Loop-Helix Proteins in the Clawed Frogs' Genomes With Common Essential Pathways and Enriched Gene Ontology Terms

Liu

2019

American Journal of Biochemistry and Biotechnology

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The international Gene Ontology (GO) and pathway databases were used to functionally analyze the clawed frogs' Basic Helix-Loop-Helix (bHLH) transcription factors of Xenopus tropicalis and Xenopus laevis in a updated genome-wide survey. There were 41 GO terms and one pathway significantly enriched for Xenopus tropicalis, whereas there were 45 GO terms and 3 pathways significantly enriched for Xenopus laevis. Among those significantly enriched GO terms, the two clawed frogs share 31 common functional GO annotations of these bHLH genes, including DNA-dependent transcription and (negative) transcription regulation, DNA binding and bHLH binding, transcription factor complex and protein heterodimerization activity, (negative) regulation of RNA metabolic processes, nuclear translocator and repressor, myogenic basic muscle-specific protein, neurogenic differentiation factor and NeuroD. Furthermore, these frogs' bHLH genes were also found to play important roles in the regulation of gene expression in some important developmental or physiological processes, such as (skeletal) muscle cell differentiation, muscle organ development, biological rhythms and rhythmic process, hypoxia (adaption) and hypoxia-inducible factors, neurogenesis, neural tube development and neurogenic differentiation, whereas they were commonly significantly enriched in TGF-beta signaling pathway. These resulted data and information are very important for us to understand the functions, classification and evolution of frog bHLH genes.

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“…USP9X can control the monoubiquitination of SMAD4 to regulate TGFβ-mediated cancer metastasis [83]. According to previous studies, USPs are crucial for the regulation of the TGFβ-mediated pathway [84].…”

Section: Usps Regulate Related Pathways To Control Cancer Metastasismentioning

confidence: 96%

The role of ubiquitin-specific peptidases in cancer progression

et al. 2019

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Protein ubiquitination is an important mechanism for regulating the activity and levels of proteins under physiological conditions. Loss of regulation by protein ubiquitination leads to various diseases, such as cancer. Two types of enzymes, namely, E1/E2/E3 ligases and deubiquitinases, are responsible for controlling protein ubiquitination. The ubiquitin-specific peptidases (USPs) are the main members of the deubiquitinase family. Many studies have addressed the roles of USPs in various diseases. An increasing number of studies have indicated that USPs are critical for cancer progression, and some USPs have been used as targets to develop inhibitors for cancer prevention. Herein we collect and organize most of the recent studies on the roles of USPs in cancer progression and discuss the development of USP inhibitors for cancer therapy in the future.

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TGF-β signaling pathway mediated by deubiquitinating enzymes

Cited by 43 publications

References 181 publications

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

Comparative Functional Analysis of the Basic Helix-Loop-Helix Proteins in the Clawed Frogs' Genomes With Common Essential Pathways and Enriched Gene Ontology Terms

The role of ubiquitin-specific peptidases in cancer progression

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