AI Article Synopsis
- A detailed understanding of cell regulation requires exploring short protein motifs that facilitate signaling, as current knowledge is mostly based on individual experimental studies.
- Recent advancements in bioinformatics tools will enhance the investigation of these motifs and disordered regions in regulatory proteins, alongside high throughput methods like phosphoproteomics.
- The review highlights linear motif biology, emphasizing that regulatory protein complexes are dynamic and cooperative, suggesting that models of cell regulatory networks should balance between stochastic and deterministic approaches.
Article Abstract
It is now clear that a detailed picture of cell regulation requires a comprehensive understanding of the abundant short protein motifs through which signaling is channeled. The current body of knowledge has slowly accumulated through piecemeal experimental investigation of individual motifs in signaling. Computational methods contributed little to this process. A new generation of bioinformatics tools will aid the future investigation of motifs in regulatory proteins, and the disordered polypeptide regions in which they frequently reside. Allied to high throughput methods such as phosphoproteomics, signaling networks are becoming amenable to experimental deconstruction. In this review, we summarise the current state of linear motif biology, which uses low affinity interactions to create cooperative, combinatorial and highly dynamic regulatory protein complexes. The discrete deterministic properties implicit to these assemblies suggest that models for cell regulatory networks in systems biology should neither be overly dependent on stochastic nor on smooth deterministic approximations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2741/3175 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanisms for DNA Interplay in Eukaryotic Transcription Factors.
Annu Rev Biophys
January 2025
1CREST Center for Cellular and Biomolecular Machines, University of California, Merced, California, USA; email:
Like their prokaryotic counterparts, eukaryotic transcription factors must recognize specific DNA sites, search for them efficiently, and bind to them to help recruit or block the transcription machinery. For eukaryotic factors, however, the genetic signals are extremely complex and scattered over vast, multichromosome genomes, while the DNA interplay occurs in a varying landscape defined by chromatin remodeling events and epigenetic modifications. Eukaryotic factors are rich in intrinsically disordered regions and are also distinct in their recognition of short DNA motifs and utilization of open DNA interaction interfaces as ways to gain access to DNA on nucleosomes.
View Article and Find Full Text PDFOrgan-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.
Sci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
View Article and Find Full Text PDFBacterial sensor evolved by decreasing complexity.
Proc Natl Acad Sci U S A
February 2025
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Granada 18008, Spain.
Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by signal binding to ligand-binding domains (LBDs). Cache domains are omnipresent LBDs found in bacteria, archaea, and eukaryotes, including humans.
View Article and Find Full Text PDF2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.
Metab Brain Dis
January 2025
Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.
View Article and Find Full Text PDFSpectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid.
Endocr Relat Cancer
January 2025
A Nikitski, Department of Pathology, University of Pittsburgh, Pittsburgh, 15261, United States.
Approximately 10-20% of thyroid cancers are driven by gene fusions, which activate oncogenic signaling through aberrant overexpression, ligand-independent dimerization, or loss of inhibitory motifs. We identified 13 thyroid tumors with thyroglobulin (TG) gene fusions and aimed to assess their histopathology and the fusions' oncogenic and tumorigenic properties. Of 11 cases with surgical pathology, 82% were carcinomas and 18% noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!