{"title":"Recent Trends in Development of Novel Therapeutics for Modulation of 14-3-3 Protein-Protein Interactions in Diseases.","authors":"Arshia Nazir","doi":"10.2174/0109298665330728241025082011","DOIUrl":null,"url":null,"abstract":"<p><p>14-3-3s constitute a group of proteins belonging to the phosphoserine/phosphothreonine family that are involved in the regulation of several physiological pathways by interacting with several client proteins. All the eukaryotic cells are known to possess 14-3-3 isoforms. In addition, 14-3-3s isolated from different eukaryotic cells share high sequence homology with each other. Seven isoforms (β, γ, ε, η, ζ, σ, and τ/θ) have been yet identified in mammals. These proteins participate in several physiological processes by either stimulating or interfering with the enzymatic activities of binding partners. These proteins take part in several human diseases upon dysregulation which include cancer and neurodegenerative disorders. Recently, a number of evidences suggest that the interaction of 14-3-3s with either oncogenic or pro-apoptotic proteins can lead to cancer development in animals. In the case of neurodegenerative disorders, 14-3-3s interact with Lewy bodies and neurofibrillary tangles in Parkinson's and Alzheimer's diseases, respectively. The current review focuses on strategies to regulate 14-3-3s' proteins in diseases. Potential strategies to regulate 14-3-3 interactions in disease conditions include the use of small interfering RNAs (siRNA), microRNA (miRNA), and modifications of 14-3-3s or their client proteins. In addition, some peptides or chemicals can also serve as potential inhibitors of 14-3-3. However, optimization of these therapeutic strategies is required for their practical implementations.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein and Peptide Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0109298665330728241025082011","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
14-3-3s constitute a group of proteins belonging to the phosphoserine/phosphothreonine family that are involved in the regulation of several physiological pathways by interacting with several client proteins. All the eukaryotic cells are known to possess 14-3-3 isoforms. In addition, 14-3-3s isolated from different eukaryotic cells share high sequence homology with each other. Seven isoforms (β, γ, ε, η, ζ, σ, and τ/θ) have been yet identified in mammals. These proteins participate in several physiological processes by either stimulating or interfering with the enzymatic activities of binding partners. These proteins take part in several human diseases upon dysregulation which include cancer and neurodegenerative disorders. Recently, a number of evidences suggest that the interaction of 14-3-3s with either oncogenic or pro-apoptotic proteins can lead to cancer development in animals. In the case of neurodegenerative disorders, 14-3-3s interact with Lewy bodies and neurofibrillary tangles in Parkinson's and Alzheimer's diseases, respectively. The current review focuses on strategies to regulate 14-3-3s' proteins in diseases. Potential strategies to regulate 14-3-3 interactions in disease conditions include the use of small interfering RNAs (siRNA), microRNA (miRNA), and modifications of 14-3-3s or their client proteins. In addition, some peptides or chemicals can also serve as potential inhibitors of 14-3-3. However, optimization of these therapeutic strategies is required for their practical implementations.
期刊介绍：
Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations.
Protein & Peptide Letters focuses on:
Structure Studies
Advances in Recombinant Expression
Drug Design
Chemical Synthesis
Function
Pharmacology
Enzymology
Conformational Analysis
Immunology
Biotechnology
Protein Engineering
Protein Folding
Sequencing
Molecular Recognition
Purification and Analysis
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