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Transcription factors are proteins that bind to DNA to regulate gene expression via transcription: the process by which the genetic code generates mRNAs or small RNAs. Transcription factors operate by various methods, for example, by modulating the binding of RNA polymerase or by recruiting coactivator or corepressor proteins to the DNA.
NRF2 enables tumor cells to tolerate oxidative and metabolic stress. A covalent molecular glue restores degradation of NRF2 by stabilizing the KEAP1–ubiquitin ligase complex.
Hur and colleagues review recent developments to provide insights into the molecular mechanisms and regulatory functions of the transcriptional regulators FOXP3 and AIRE.
DNA G-quadruplex (G4) structures can form at regulatory regions of transcriptionally active genes in open chromatin and are abundant in cancer states, but targeting G4-binding proteins in their native chromatin environment is challenging. Now bifunctional molecules that bind naturally occurring G4 sites and recruit ubiquitination machinery facilitate the degradation of G4-specific transcription factors and chromatin remodellers.
The identification and optimization of bifunctional small-molecule protein degraders remain labor-intensive processes largely restricted to proteins with well-defined ligandable pockets. Here, the authors present a polymer-based strategy, HYbrid DegRAding Copolymer (HYDRAC): modular copolymers that densely display target-binding peptides in conjunction with peptide-based or small molecule-derived degrons in a multivalent fashion, enabling selective degradation of disease-relevant proteins.
Determining the consequences of acetylation for a protein of interest in cells is a considerable challenge. Using genetic code expansion and p53, this study shows that site-specific incorporation of non-hydrolysable acetyllysine analogues enables functional analysis.
Activation of genes depends on transcription factors and chromatin remodelers. Here, the authors show ARID1A organizes these components through phase separation, co-condensing with specific transcription factors to maintain chromatin accessibility and drive gene expression.
Here, the authors demonstrate that VGLL4 maintains cartilage integrity by forming a complex with TEAD4-SMAD3 to regulate extracellular matrix homeostasis. VGLL4 deficiency accelerates osteoarthritis, while its restoration or SMAD3 delivery rescues cartilage damage, suggesting therapeutic potential.
NRF2 enables tumor cells to tolerate oxidative and metabolic stress. A covalent molecular glue restores degradation of NRF2 by stabilizing the KEAP1–ubiquitin ligase complex.
A complex of the NF-κB family member p52 and the transcription factor ETS1 is required for B cell germinal center responses to T cell-dependent immunization and for IgE-dependent allergic responses.
Genes in transcription factor families presumably arose to accommodate the increasingly complex regulatory needs of multicellular organisms. A study now identifies the basis for distinction between the NF-κB family members Rel and RelA.
The androgen receptor forms nuclear condensates associated with gene transcription. Investigating the molecular basis of condensate formation led us to discover an approach for optimizing small molecules that inhibit the receptor in a currently untreatable form of prostate cancer.
