Tumor suppressor candidate 2 (TUSC2) (TUSC2)

Tumor suppressor candidate 2 (TUSC2), also known as FUS1, is a 110-amino-acid protein encoded by a gene at the frequently deleted 3p21.3 chromosomal region in lung cancers and other malignancies. It functions as a regulator of mitochondrial calcium handling, facilitating calcium uptake into mitochondria, which influences reactive oxygen species production, mitochondrial membrane potential, permeability transition pore opening, and glutathione redox status. TUSC2 deficiency impairs calcium-coupled processes, leading to dysregulated mitochondrial homeostasis in epithelial, splenocyte, and T cells, including altered NF-κB and NFAT pathway activation during CD4+ T-cell responses. In disease contexts, TUSC2 loss promotes tumor formation (e.g., lung cancer, lymphomas), chronic inflammation, and autoimmune-like syndromes resembling systemic lupus erythematosus, with heightened Th1 differentiation, proliferation, and surface expression of PD-1/PD-L1. No approved drugs directly target TUSC2, but phase I trials of systemic TUSC2 gene therapy in advanced lung cancer demonstrated restored expression, apoptosis induction in tumors, and manageable toxicities.

Other names

FUS1Fus1Fusion 1 proteinFus-1 proteinC3ORF11

Gene replacement therapy to restore TUSC2 expression, upregulating intrinsic apoptosis pathway in cancer cells