Synaptic nuclear envelope protein 2 (Nesprin-2) (SYNE2)

Synaptic nuclear envelope protein 2 (Nesprin-2), encoded by the SYNE2 gene, is a large scaffolding protein that forms the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex at the nuclear envelope (UniProt, 2024). It physically connects the nuclear lamina to the actin cytoskeleton, playing a vital role in nuclear positioning, maintaining nuclear morphology, and facilitating mechanotransduction (PubMed, 2015). Mutations in SYNE2 are primarily linked to Emery-Dreifuss muscular dystrophy 5 (EDMD5) and dilated cardiomyopathy, where disrupted nucleo-cytoskeletal coupling leads to cellular fragility and impaired signaling (NIH, 2018). In oncology, Nesprin-2 is often dysregulated; it is upregulated in glioblastoma, contributing to tumor progression and migration, while its downregulation in colorectal cancer affects cell adhesion (PubMed, 2023; NIH, 2011). While no specific drugs are currently approved to target Nesprin-2, research indicates that Sulindac sulfide can downregulate its expression in colorectal cancer cells (NIH, 2011). Additionally, disrupting the LINC complex via dominant-negative constructs or shRNA-mediated knockdown has shown potential in reducing glioblastoma growth in preclinical models (Oxford Academic, 2023).

Other names

SYNE2KASH2NUANCESyne-2Nesprin 2Nucleus and actin connecting element proteinNuclear envelope spectrin repeat protein 2

Downregulation of protein expression and disruption of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.