Leire Torices, Caroline E. Nunes-Xavier, Rafael Pulido
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引用次数: 0
Abstract
Tumor suppressor genes are frequently targeted by mutations introducing premature termination codons (PTC) in the protein coding sequence, both in sporadic cancers and in the germline of patients with cancer predisposition syndromes. These mutations have a high pathogenic impact since they generate C-terminal truncated proteins with altered stability and function. In addition, PTC mutations trigger transcript degradation by nonsense-mediated mRNA decay. Suppression of PTC by translational readthrough restores protein biosynthesis and stabilizes the PTC-targeted mRNA, making a suitable therapeutic approach the reconstitution of active full-length tumor suppressor proteins by pharmacologically-induced translational readthrough. Here, we review the recent advances in small molecule pharmacological induction of translational readthrough of disease-associated PTC from tumor suppressor genes, and discuss the therapeutic potential of translational readthrough in specific groups of patients with hereditary syndromic cancers.
期刊介绍:
IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.