Cellular G-quadruplex-binding protein (G4BP)

Cellular G-quadruplex-binding proteins (G4BPs) are a diverse class of proteins that specifically recognize and interact with G-quadruplex (G4) structures, which are non-canonical four-stranded nucleic acid arrangements formed in guanine-rich regions of DNA or RNA (Nature Reviews Chemistry, 2021) [1]. These proteins are functionally categorized into those that stabilize G4s, those that resolve or unwind them—such as the helicases DHX36 and WRN—and those that utilize G4s as recruitment scaffolds for downstream signaling and regulatory complexes (Journal of Medicinal Chemistry, 2020) [2]. G4BPs are essential for regulating fundamental biological processes, including telomere maintenance, DNA replication, the transcription of key oncogenes like MYC and BCL2, and the translation of specific mRNAs (Nucleic Acids Research, 2015) [3]. In oncology, the dysregulation of G4-protein interactions is frequently linked to genomic instability and the sustained expression of proliferative genes, while in neurodegenerative diseases, G4BPs like FUS and TDP-43 are implicated in the formation of toxic RNA-protein aggregates (FEBS Letters, 2015) [4]. Therapeutic strategies involve using small-molecule G4 ligands, such as Pidnarulex (CX-5461), to disrupt G4BP binding or trap these proteins on DNA, thereby inducing site-specific DNA damage and apoptosis in cancer cells (Nature Communications, 2017) [5]. Despite their therapeutic potential, a primary challenge in targeting G4BPs lies in achieving selectivity across the thousands of G4 structures present in the human genome to minimize off-target effects and systemic toxicity (Nature Reviews Drug Discovery, 2011) [6].

Other names

G-quadruplex-interacting proteinG4-binding proteinG4-recognizing proteinG-quadruplex ligand-binding protein

Modulation of G-quadruplex stability, competitive inhibition of protein-G4 binding, induction of DNA damage response, and transcriptional interference through G4-structure stabilization or resolution.