title: Functional conservation and innovation of amphioxus RIP1-mediated signaling in cell fate determination.
abstract: Recently, receptor interacting protein (RIP)-1 has been recognized as an intracellular sensor at the crossroads of apoptosis, necroptosis, and cell survival. To reveal when this crucial molecule originated and how its function in integrating stress signals evolved, in this study we report on two RIP1 homologs in Chinese amphioxus (Branchiostoma belcheri tsingtauense), designated B. belcheri tsingtauense RIP1a and B. belcheri tsingtauense RIP1b. Phylogenetic analysis indicates that they are generated by domain recombination and lineage-specific duplication. Similar to human RIP1, both B. belcheri tsingtauense RIP1a and B. belcheri tsingtauense RIP1b activate NF-κB in a kinase activity-independent manner and induce apoptosis through the Fas-associated death domain protein-caspase cascade. Moreover, we found that the natural point mutation of Q to I in the RIP homotypic interaction motif of B. belcheri tsingtauense RIP1a provides negative feedback for amphioxus RIP1-mediated signaling. Thus, our study not only suggests that RIP1 has emerged as a molecular switch in triggering cell death or survival in a basal chordate, but also adds new insights into the regulation mechanisms of RIP1-related signaling, providing a novel perspective on human diseases mediated by RIP1.
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen Zhongshan University, Guangzhou 510275, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Shaochun
authors.initials: S
authors.lastname: Yuan
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Huang
authors.forename: Guangrui
authors.initials: G
authors.lastname: Huang
authors.forename: Manyi
authors.initials: M
authors.lastname: Yang
authors.forename: Liqun
authors.initials: L
authors.lastname: Xu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Renwei
authors.initials: R
authors.lastname: Zhang
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Yu
authors.forename: Shangwu
authors.initials: S
authors.lastname: Chen
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D019070:Cell Lineage; D002470:Cell Survival / Q000235:genetics*; D002816:Chordata, Nonvertebrate; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010802:Phylogeny; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection
chemical_list: D053422:Receptor-Interacting Protein Serine-Threonine Kinases