RIP3 β and RIP3 γ, two novel splice variants of receptor-interacting protein 3 (RIP3), downregulate RIP3-induced apoptosis

Receptor-interacting protein 3 (RIP3) is an apoptosis inducing member of the RIP family. Here we report two novel splice variants of human RIP3, designated RIP3 β and RIP3 γ respectively. Unlike full-length RIP3, both variants possess a truncated N-terminal kinase domain and a distinct and shorter C terminus, and therefore abrogate nucleocytoplasmic shuttling and apoptosis-inducing activity. Transient expression of either variant was found to downregulate RIP3-mediated apoptosis. Importantly, real-time PCR analysis reveals that the ratio of RIP3 γ to RIP3 is significantly increased in colon and lung cancers relative to their matched normal tissues, indicating that RIP3 γ might be a major splice form associated with tumorigenesis.