Srebrow Anabella, Kornblihtt Alberto R
Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, (C1428EHA) Buenos Aires, Argentina.
J Cell Sci. 2006 Jul 1;119(Pt 13):2635-41. doi: 10.1242/jcs.03053.
Alternative splicing is a crucial mechanism for generating protein diversity. Different splice variants of a given protein can display different and even antagonistic biological functions. Therefore, appropriate control of their synthesis is required to assure the complex orchestration of cellular processes within multicellular organisms. Mutations in cis-acting splicing elements or changes in the activity of constitutive or alternative splicing could have a profound regulatory proteins that compromise the accuracy of either impact on human pathogenesis, in particular in tumor development and progression. Mutations in splicing elements, for example, have been found in genes such as LKB1, KIT, CDH17, KLF6 and BRCA1, and changes in trans-acting regulators can affect the expression of genes such as Ron, RAC1 and CD44.
可变剪接是产生蛋白质多样性的关键机制。给定蛋白质的不同剪接变体可表现出不同甚至拮抗的生物学功能。因此，需要对其合成进行适当控制，以确保多细胞生物体内细胞过程的复杂协调。顺式作用剪接元件的突变或组成型或可变剪接活性的变化可能对人类发病机制产生深远影响，特别是在肿瘤发生和发展过程中。例如，在LKB1、KIT、CDH17、KLF6和BRCA1等基因中发现了剪接元件的突变，反式作用调节因子的变化可影响Ron、RAC1和CD44等基因的表达。
