کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5521137 | 1401250 | 2017 | 22 صفحه PDF | دانلود رایگان |
- The atomic-level structures of G-quadruplexes in BCL-2 promoter/transcripts are described.
- G-quadruplexes contribute to cellular processes and oncogenic transformation of BCL-2.
- Recent pharmacological advances in quadruplex-targeting molecules are discussed.
- Quadruplex-based therapy overcomes the limitations of BCL-2 protein-based therapy.
- The promises and challenges of BCL-2 quadruplex-based therapies are examined.BCL-2 overexpression promotes neoplastic cell expansion in cancers. Multiple noncanonical B-DNA motifs in the BCL-2 gene regulate selective modulation of its expression in normal and cancer cells. Three G-quadruplex topologies and one i-motif, in the vicinity of the P1 (major) promoter, stringently control its transcription. RNA quadruplexes and Z-DNA elements within translocation breakpoints of noncoding regions affect translation and promote oncogenic transformation of BCL-2 [e.g., t(14;18) translocation]. These structures, therefore, suggest promising targets in gene-directed anticancer therapeutics. This review summarizes structural and mechanistic aspects of G-quadruplexes, and recent pharmacological advances in BCL-2-quadruplex-targeted drug design together with prospects and challenges in cancer treatment.
Journal: Drug Discovery Today - Volume 22, Issue 8, August 2017, Pages 1165-1186