NRF2 is a well-known, master transcription factor (TF) of oxidative and xenobiotic stress responses. Recent studies uncovered an even wider regulatory role of NRF2 influencing carcinogenesis, inflammation and neurodegeneration. Prompted by these advances here we present a systems-level resource for NRF2 interactome and regulome that includes 289 protein-protein, 7469 TF-DNA and 85 miRNA interactions. As systems-level examples of NRF2-related signaling we identified regulatory loops of NRF2 interacting proteins (e.g., JNK1 and CBP) and a fine-tuned regulatory system, where 35 TFs regulated by NRF2 influence 63 miRNAs that down-regulate NRF2. The presented network and the uncovered regulatory loops may facilitate the development of efficient, NRF2-based therapeutic agents.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511993PMC
http://dx.doi.org/10.1016/j.febslet.2012.05.016DOI Listing

Publication Analysis

Top Keywords

interactome regulome
8
loops nrf2
8
regulatory loops
8
nrf2
6
nrf2-related interactome
4
regulome multifunctional
4
multifunctional proteins
4
proteins fine-tuned
4
fine-tuned autoregulatory
4
autoregulatory loops
4

Similar Publications

Article Synopsis
  • Research in population genetics has historically focused on European ancestry, but global studies like the 1000 Genomes Project highlight genetic variations across different ethnic groups.
  • A new concept, "edgotype," examines how mutations impact protein interactions, and this study used a semi-supervised learning approach to analyze ~50,000 non-synonymous SNVs and their functional roles.
  • Findings suggest that many variants found in healthy populations can alter protein interactions, potentially explaining differences in disease susceptibility among populations and revealing insights into genetic diversity.
View Article and Find Full Text PDF

Cancer research calls for new approaches that account for the regulatory complexities of biology. We present, in this study, the differential transcriptional regulome (DIFFREG) approach for the identification and prioritization of key transcriptional regulators and apply it to the case of renal cell carcinoma (RCC) biology. Of note, RCC has a poor prognosis and the biomarker and drug discovery studies to date have tended to focus on gene expression independent from mutations and/or post-translational modifications.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of cognitive decline. The alarming epidemiological features of Alzheimer's disease, combined with the high failure rate of candidate drugs tested in the preclinical phase, impose more intense investigations for new curative treatments. NRF2 (Nuclear factor-erythroid factor 2-related factor 2) plays a critical role in the inflammatory response and in the cellular redox homeostasis and provides cytoprotection in several diseases including those in the neurodegeneration spectrum.

View Article and Find Full Text PDF

Genomic innovation and regulatory rewiring during evolution of the cotton genus Gossypium.

Nat Genet

December 2022

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, China.

Phenotypic diversity and evolutionary innovation ultimately trace to variation in genomic sequence and rewiring of regulatory networks. Here, we constructed a pan-genome of the Gossypium genus using ten representative diploid genomes. We document the genomic evolutionary history and the impact of lineage-specific transposon amplification on differential genome composition.

View Article and Find Full Text PDF

A Quantum Vaccinomics Approach Based on Protein-Protein Interactions.

Methods Mol Biol

January 2022

SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo s/n, Ciudad Real, Spain.

Vaccines are the most effective preventive intervention to reduce the impact of infectious diseases worldwide. In particular, tick-borne diseases represent a growing burden for human and animal health worldwide and vaccines are the most effective and environmentally sound approach for the control of vector infestations and pathogen transmission. However, the development of effective vaccines for the control of tick-borne diseases with combined vector-derived and pathogen-derived antigens is one of the limitations for the development of effective vaccine formulations.

View Article and Find Full Text PDF

Want 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!