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Molecular and Cellular Factors Regulating Signal Transduction, Diseases, and Stem Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 10777

Special Issue Editor


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Guest Editor
Department of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea
Interests: oncogenes and tumor suppressor genes mediated carcinogenesis; signal transduction related to ubiquitination and deubiquitination; factors affecting stem cell maintenance and differentiation; post-translational modifications of transcriptional factors during odontogenesis; genome editing on stem cells to generate several disease models using CRISPR/Cas9 system

Special Issue Information

Dear Colleagues,

An upsurge of knowledge on the molecular and cellular mechanisms that mediate cancer and other diseases has been reported in recent years. Although several diseases, including cancer, have been identified as occurring for over a million years, the search for effective treatment for most of the diseases that target the molecular and cellular pathways has not been successful. Several cellular targets have been investigated for the treatment of human diseases, including transcription factors, epigenetic targeting of oncogenes and tumor suppressors, and post-translational regulators. Understanding how the molecular mechanism of certain genes causes diseases, including the transformation from normal cells to cancer cells, is very essential.

On another note, there are several transcriptional factors which determine the stem cell’s fate. Among them, post-translational modification by ubiquitin molecules is a key regulatory process for the determination of a stem cell’s fate. Ubiquitination and deubiquitination are the major cellular processes used to balance the protein turnover of several transcription factors that regulate stem cell differentiation. The ubiquitination level of proteins is determined by the balance of E3 ubiquitin ligases and DUBs, which determine protein stability. The ubiquitination and deubiquitination molecular switches must operate in a balanced manner to control the ubiquitin pool, and maintain protein homeostasis and cellular functions. The actions of E3 ligases and DUBs are associated with the development and progress of tumorigenesis by modifying key proteins that regulate the cell cycle, gene transcription, DNA repair, and apoptosis. Similarly, ubiquitination and deubiquitination, which regulate the protein turnover of several stemness-related proteins, must be carefully coordinated to ensure optimal embryonic stem cell maintenance and differentiation.

 

This Special Issue welcomes both original papers and review articles addressing one or more of the above issues, or any of the topics mentioned in the key words below.

Dr. Suresh Ramakrishna
Guest Editor

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Keywords

  • Oncogenes and tumor suppressors
  • Ubiquitin-proteasome pathway
  • Protein degradation and protein stability
  • Pre-clinical research and Clinical trials
  • Anti-cancer drug
  • Drug resistance
  • Cancer pathogenesis and therapeutics
  • Enzymatic functions
  • Cell cycle regulation
  • DNA damage, DNA repair and Cell death
  • Stem cells regulation and differentiation
  • Transcriptional factors regulation
  • Disease association and progression

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Published Papers (3 papers)

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Research

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15 pages, 2507 KiB  
Article
Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation
by Kamini Kaushal, Apoorvi Tyagi, Janardhan Keshav Karapurkar, Eun-Jung Kim, Parthasaradhireddy Tanguturi, Kye-Seong Kim, Han-Sung Jung and Suresh Ramakrishna
Int. J. Mol. Sci. 2022, 23(2), 856; https://doi.org/10.3390/ijms23020856 - 13 Jan 2022
Cited by 8 | Viewed by 2796
Abstract
The osteoblast differentiation capacity of mesenchymal stem cells must be tightly regulated, as inadequate bone mineralization can lead to osteoporosis, and excess bone formation can cause the heterotopic ossification of soft tissues. The balanced protein level of Msh homeobox 1 (MSX1) is critical [...] Read more.
The osteoblast differentiation capacity of mesenchymal stem cells must be tightly regulated, as inadequate bone mineralization can lead to osteoporosis, and excess bone formation can cause the heterotopic ossification of soft tissues. The balanced protein level of Msh homeobox 1 (MSX1) is critical during normal osteogenesis. To understand the factors that prevent MSX1 protein degradation, the identification of deubiquitinating enzymes (DUBs) for MSX1 is essential. In this study, we performed loss-of-function-based screening for DUBs regulating MSX1 protein levels using the CRISPR/Cas9 system. We identified ubiquitin-specific protease 11 (USP11) as a protein regulator of MSX1 and further demonstrated that USP11 interacts and prevents MSX1 protein degradation by its deubiquitinating activity. Overexpression of USP11 enhanced the expression of several osteogenic transcriptional factors in human mesenchymal stem cells (hMSCs). Additionally, differentiation studies revealed reduced calcification and alkaline phosphatase activity in USP11-depleted cells, while overexpression of USP11 enhanced the differentiation potential of hMSCs. These results indicate the novel role of USP11 during osteogenic differentiation and suggest USP11 as a potential target for bone regeneration. Full article
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Review

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21 pages, 1492 KiB  
Review
Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases
by Jin-Taek Hwang, Ahyoung Lee and Changwon Kho
Int. J. Mol. Sci. 2022, 23(9), 5053; https://doi.org/10.3390/ijms23095053 - 2 May 2022
Cited by 31 | Viewed by 3988
Abstract
Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and [...] Read more.
Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and physiological processes by altering the activity, stability, localization, trafficking, or interaction networks of its target molecules. The Ub/Ubl modification is tightly regulated as a multi-step enzymatic process by enzymes specific to this family. There is growing evidence that the dysregulation of Ub/Ubl modifications is associated with various diseases, providing new targets for drug development. In this review, we summarize the recent progress in understanding the roles and therapeutic targets of the Ub and Ubl systems in the onset and progression of human diseases, including cancer, neurodegenerative disorders, and heart diseases. Full article
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10 pages, 2219 KiB  
Review
Regulatory Processes of the Canonical Wnt/β-Catenin Pathway and Photobiomodulation in Diabetic Wound Repair
by Sandy Winfield Jere and Nicolette Nadene Houreld
Int. J. Mol. Sci. 2022, 23(8), 4210; https://doi.org/10.3390/ijms23084210 - 11 Apr 2022
Cited by 8 | Viewed by 3325
Abstract
Skin is a biological system composed of different types of cells within a firmly structured extracellular matrix and is exposed to various external and internal insults that can break its configuration. The restoration of skin’s anatomic continuity and function following injury is a [...] Read more.
Skin is a biological system composed of different types of cells within a firmly structured extracellular matrix and is exposed to various external and internal insults that can break its configuration. The restoration of skin’s anatomic continuity and function following injury is a multifaceted, dynamic, well-coordinated process that is highly dependent on signalling pathways, including the canonical Wnt/β catenin pathway, all aimed at restoring the skin’s protective barrier. Compromised and inappropriate tissue restoration processes are often the source of wound chronicity. Diabetic patients have a high risk of developing major impediments including wound contamination and limb amputation due to chronic, non-healing wounds. Photobiomodulation (PBM) involves the application of low-powered light at specific wavelengths to influence different biological activities that incite and quicken tissue restoration. PBM has been shown to modulate cellular behaviour through a variety of signal transduction pathways, including the Wnt/β catenin pathway; however, the role of Wnt/β catenin in chronic wound healing in response to PBM has not been fully defined. This review largely focuses on the role of key signalling pathways in human skin wound repair, specifically, the canonical Wnt/β-catenin pathway, and the effects of PBM on chronic wound healing. Full article
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