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Myc-associated zinc-finger protein (MAZ) is a transcription factor characterized by its Cys2His2-type zinc finger domains, which facilitate binding to GA-rich sequences in gene promoters (UniProt: P35270). It plays a critical role in regulating the expression of several key genes, most notably the MYC proto-oncogene, as well as genes involved in cell cycle progression and inflammation (NCBI Gene: 4150). In oncology, MAZ is frequently overexpressed and acts as a driver for tumor growth, metastasis, and angiogenesis in cancers such as prostate, breast, and glioblastoma (PMID: 25605116). Beyond cancer, MAZ (also known as SAF-1) is involved in the inflammatory response by inducing the expression of serum amyloid A, linking it to chronic inflammatory diseases and amyloidosis (PMID: 11500516). While traditionally considered difficult to target, current therapeutic strategies focus on using small molecules like TMPyP4 to stabilize G-quadruplex structures in promoters to prevent MAZ binding or employing nucleic acid-based inhibitors (PMID: 18410171). Its ubiquitous expression presents a challenge for drug development, as systemic inhibition may lead to significant off-target toxicities.
Inhibition of DNA binding to promoter regions through G-quadruplex stabilization and transcriptional repression of oncogenes
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