ijms-logo

Journal Browser

Journal Browser

Proteins in Human Diseases: Molecular Insights into Drug Targets and Novel Therapeutic Modalities

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 (28 February 2021) | Viewed by 19029

Special Issue Editors

Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35233, USA
Interests: protein therapeutics; protein structure and functions; protein-protein interactions; drug targets; angiogenesis; pro-and anti-angiogenic factors; hormonal receptors; hormone-related cancers; prostate cancer; breast cancer; active and passive immunotherapy; antibody engineering
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Korea
Interests: RNA biology; immunotherapy

Special Issue Information

Dear Colleagues,

Proteins are fundamental biomolecules that modulate diverse cellular and molecular events in living organisms. Scientific studies have established that aberrant levels of proteins due to the dysregulation of gene transcription cause various pathophysiological dysfunctions in humans. In this regard, tremendous scientific endeavors and translational research efforts have been made to identify the functions of the involved proteins and to develop treatment modalities for disease management. 

For last two decades, both academic and industrial communities have witnessed the huge success of immunotherapy in harnessing both passive (e.g., therapeutic antibodies) and active immune activators (e.g., cancer vaccines, CAR-T and NK cell therapy), which suggests a great potential of protein therapeutics and biologics for the treatment of multiple human diseases. Furthermore, scientific advances in structural and protein chemistry (e.g., cryo-EM), molecular genetics (e.g., NGS), and cellular biology (e.g., single-cell analysis) enable us to revisit original findings and initial clinical observations on incurable diseases, which may lead our research on the etiology and therapy options for these diseases in a whole new direction. Therefore, there is a compelling need to identify novel functions of proteins and orphan receptors to promote a new type of research.    

This Special Issue will collect reviews, perspectives and opinions, and research articles covering various topics, with the aim to present less known molecular aspects of proteins that can be targeted to develop novel therapy modalities for various diseases. In this regard, as a former scientist in an academic institution and a current primary investigator in the industry, the editor urges his Colleagues to communicate outstanding research findings for publication in this Special Issue as a valuable contribution to protein science.

Dr. Joo Hyoung Lee
Dr. Tae-Don Kim
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Protein structure;
  • Protein–protein interaction;
  • Ligand–receptor interaction;
  • Newly identified protein function;
  • Orphan receptors;
  • Therapy resistance;
  • Signal transduction;
  • Target proteins and clinical relevance;
  • Protein therapeutics & biologic;
  • Peptide therapeutics;
  • Antibody therapeutics;
  • Immunotherapy;
  • Human diseases;
  • Cancer

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

11 pages, 17281 KiB  
Article
Multiple Immunostainings with Different Epitope Retrievals—The FOLGAS Protocol
by Anna von Schoenfeld, Peter Bronsert, Michael Poc, Andrew Fuller, Andrew Filby, Stefan Kraft, Konrad Kurowski, Kristin Sörensen, Julia Huber, Jens Pfeiffer, Michele Proietti, Verena Stehl, Martin Werner and Maximilian Seidl
Int. J. Mol. Sci. 2022, 23(1), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010223 - 25 Dec 2021
Cited by 1 | Viewed by 2971
Abstract
We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of [...] Read more.
We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections. Full article
Show Figures

Figure 1

Review

Jump to: Research

13 pages, 4146 KiB  
Review
Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target
by Young Ha Ahn, Se-Chan Oh, Shengtao Zhou and Tae-Don Kim
Int. J. Mol. Sci. 2021, 22(9), 4523; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094523 - 26 Apr 2021
Cited by 11 | Viewed by 3333
Abstract
Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as [...] Read more.
Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as a pharmacological target and therapeutic. However, WRS is still generally regarded simply as an enzyme that produces Trp in polypeptides; therefore, studies of the pharmacological effects, therapeutic targets, and mechanisms of action of WRS are still at an emerging stage. This review summarizes the involvement of WRS in human diseases. We hope that this will encourage further investigation into WRS as a potential target for drug development in various pathological states including infection, tumorigenesis, and autoimmune and brain diseases. Full article
Show Figures

Figure 1

17 pages, 19307 KiB  
Review
Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases
by Soeun Hwang, Min-Hee Kim and Chang-Woo Lee
Int. J. Mol. Sci. 2021, 22(7), 3791; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073791 - 06 Apr 2021
Cited by 5 | Viewed by 4282
Abstract
More than 70% of eukaryotic proteins are regulated by phosphorylation. However, the mechanism of dephosphorylation that counteracts phosphorylation is less studied. Phosphatases are classified into 104 distinct groups based on substrate-specific features and the sequence homologies in their catalytic domains. Among them, dual-specificity [...] Read more.
More than 70% of eukaryotic proteins are regulated by phosphorylation. However, the mechanism of dephosphorylation that counteracts phosphorylation is less studied. Phosphatases are classified into 104 distinct groups based on substrate-specific features and the sequence homologies in their catalytic domains. Among them, dual-specificity phosphatases (DUSPs) that dephosphorylate both phosphoserine/threonine and phosphotyrosine are important for cellular homeostasis. Ssu72 is a newly studied phosphatase with dual specificity that can dephosphorylate both phosphoserine/threonine and phosphotyrosine. It is important for cell-growth signaling, metabolism, and immune activation. Ssu72 was initially identified as a phosphatase for the Ser5 and Ser7 residues of the C-terminal domain of RNA polymerase II. It prefers the cis configuration of the serine–proline motif within its substrate and regulates Pin1, different from other phosphatases. It has recently been reported that Ssu72 can regulate sister chromatid cohesion and the separation of duplicated chromosomes during the cell cycle. Furthermore, Ssu72 appears to be involved in the regulation of T cell receptor signaling, telomere regulation, and even hepatocyte homeostasis in response to a variety of stress and damage signals. In this review, we aim to summarize various functions of the Ssu72 phosphatase, their implications in diseases, and potential therapeutic indications. Full article
Show Figures

Figure 1

15 pages, 1156 KiB  
Review
RNA Helicases as Shadow Modulators of Cell Cycle Progression
by Olga Sergeeva and Timofei Zatsepin
Int. J. Mol. Sci. 2021, 22(6), 2984; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062984 - 15 Mar 2021
Cited by 15 | Viewed by 3294
Abstract
The progress of the cell cycle is directly regulated by modulation of cyclins and cyclin-dependent kinases. However, many proteins that control DNA replication, RNA transcription and the synthesis and degradation of proteins can manage the activity or levels of master cell cycle regulators. [...] Read more.
The progress of the cell cycle is directly regulated by modulation of cyclins and cyclin-dependent kinases. However, many proteins that control DNA replication, RNA transcription and the synthesis and degradation of proteins can manage the activity or levels of master cell cycle regulators. Among them, RNA helicases are key participants in RNA metabolism involved in the global or specific tuning of cell cycle regulators at the level of transcription and translation. Several RNA helicases have been recently evaluated as promising therapeutic targets, including eIF4A, DDX3 and DDX5. However, targeting RNA helicases can result in side effects due to the influence on the cell cycle. In this review, we discuss direct and indirect participation of RNA helicases in the regulation of the cell cycle in order to draw attention to downstream events that may occur after suppression or inhibition of RNA helicases. Full article
Show Figures

Figure 1

18 pages, 859 KiB  
Review
RNA-Binding Proteins and the Complex Pathophysiology of ALS
by Wanil Kim, Do-Yeon Kim and Kyung-Ha Lee
Int. J. Mol. Sci. 2021, 22(5), 2598; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052598 - 05 Mar 2021
Cited by 11 | Viewed by 4455
Abstract
Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of [...] Read more.
Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles. Full article
Show Figures

Figure 1

Back to TopTop