Splicing Variants, Protein-Protein Interactions, and Drug Targeting in Hutchinson-Gilford Progeria Syndrome and Small Cell Lung Cancer

Alternative splicing (AS) is a biological operation that enables a messenger RNA to encode protein variants (isoforms) that give one gene several functions or properties. This process provides one of the major sources of use for understanding the proteomic diversity of multicellular organisms. In combination with post-translational modifications, it contributes to generating a variety of proteinprotein interactions (PPIs) that are essential to cellular homeostasis or proteostasis. However, cells exposed to many kinds of stresses (aging, genetic changes, carcinogens, etc.) sometimes derive cancer or disease onset from aberrant PPIs caused by DNA mutations. In this review, we summarize how splicing variants may form a neomorphic protein complex and cause diseases such as HutchinsonGilford progeria syndrome (HGPS) and small cell lung cancer (SCLC), and we discuss how proteinprotein interfaces obtained from the variants may represent efficient therapeutic target sites to treat HGPS and SCLC.

Automated summary

Alternative splicing is a biological operation that allows a gene to encode multiple protein variants with different functions, contributing to the proteomic diversity of multicellular organisms. It plays a crucial role in generating protein-protein interactions along with post-translational modifications, but aberrant interactions caused by DNA mutations can lead to cancer or diseases. This review discusses how splicing variants can form neomorphic protein complexes and contribute to diseases such as Hutchinson-Gilford progeria syndrome (HGPS) and small cell lung cancer (SCLC), and proposes that the protein-protein interfaces from these variants may serve as potential therapeutic targets for treating HGPS and SCLC.