Tuning up Transcription Factors for Therapy

Abstract

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, transcription activator-like effector (TALE) and CRISPR-dCas9 revealed common principles behind their efficacy, which can aid the optimization of transcriptional activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor natural and synthetic transcription factors to the needs of specific applications.

Transcription Factors Interplay Orchestrates the Immune-Metabolic Response of Leishmania Infected Macrophages

“…Indeed, deregulation of transcription factors is a common feature to the majority of human cancers and is involved in a large number of human diseases ( Papavassiliou and Papavassiliou, 2016 ). A better understanding of the pathologies, of the mechanisms of transcriptional regulation and their precise function as well as the development of new technologies ( Hagenbuchner and Ausserlechner, 2016 ; Hecker and Wagner, 2017 ; Becskei, 2020 ), has allowed the development of novel therapeutic strategies that target transcription factors. Different small molecules that interact in various way with transcription factors to modulate their expression, degradation, interaction with DNA or other proteins, are actually used or evaluated for cancer treatment ( Lambert et al., 2018 ).…”

Deciphering the Transcription Factor Landscape in Neuroendocrine Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation

“…Hence, a comprehensive study on the TF landscape associated with PCa is greatly warranted. Many TFs, potentially crucial in PCa progression and NE transdifferentiation, remain unidentified or inadequately studied due to their low abundance and subtle expression changes, which might indeed regulate the expression program of those "high jumper" genes (28). This presents a significant knowledge gap, particularly in understanding TFs relevant to drug resistance and lineage transition in PCa.…”

TransCRISPR - sgRNA design tool for CRISPR/Cas9 experiments targeting DNA sequence motifs

“…(1, 2). TFs recognize specific sequence motifs in DNA and by recruitment and interaction with other factors they can up- or downregulate expression of target genes (3, 4, 5). Transcription factors are a part of complex regulatory networks and any aberrations of their function may have severe consequences, e. g. carcinogenesis (6).…”