FPGS and cancer: Aberrant splicing of FPGS induced skipping of exon 12 and generated a nonfunctional FPGS enzyme, which leads to reduced retention of antifolates and causes cancer cells resistant to folate antagonist methotrexate.23 In patients with B-cell malignancies treated with adoptive T cells expressed chimeric antigen receptors against CD19 (CART-19), the expression of alternatively spliced CD19 isoform lacking exon 2 caused failure of initiation of CART-19-mediated cancer cell death.24 TGF-β-activated kinase 1 (TAK1) promoted TGF-β-induced apoptosis in response to TGF-β activation.