title: The spliceosome as a target of novel antitumour drugs.
abstract: Several bacterial fermentation products and their synthetic derivatives display antitumour activities and bind tightly to components of the spliceosome, which is the complex molecular machinery involved in the removal of introns from mRNA precursors in eukaryotic cells. The drugs alter gene expression, including alternative splicing, of genes that are important for cancer progression. A flurry of recent reports has revealed that genes encoding splicing factors, including the drug target splicing factor 3B subunit 1 (SF3B1), are among the most highly mutated in various haematological malignancies such as chronic lymphocytic leukaemia and myelodysplastic syndromes. These observations highlight the role of splicing factors in cancer and suggest that an understanding of the molecular effects of drugs targeting these proteins could open new perspectives for studies of the spliceosome and its role in cancer progression, and for the development of novel antitumour therapies.
authors.affiliation: Centre de Regulació Genòmica, Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bonnal
authors.forename: Luisa
authors.initials: L
authors.lastname: Vigevani
authors.forename: Juan
authors.initials: J
authors.lastname: Valcárcel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000378:metabolism; D018450:Disease Progression; D015195:Drug Design; D005285:Fermentation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D017381:Spliceosomes / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human