Nucleocytoplasmic shuttling of receptor-interacting protein 3 (RIP3): identification of novel nuclear export and import signals in RIP3.
Receptor-interacting protein 3 (RIP3), a member of the RIP Ser/Thr kinase family, has been characterized as a pro-apoptotic protein involved in the tumor necrosis factor receptor-1 signaling pathway. In this study, we have mapped a minimal region of RIP3 sufficient for apoptosis induction to a fragment of 31 amino acids in length. This minimal region also functions as an unconventional nuclear localization signal sufficient to confer the import of full-length RIP3 to the nucleus to trigger apoptosis, suggesting that RIP3 is able to play an apoptosis-inducing role in the nucleus. In addition, we have characterized two novel leucine-rich nuclear export signals (NESs) that are responsible for the nuclear export of RIP3 to the cytoplasm via a chromosome region maintenance 1 (CRM1)-dependent pathway and an extra leucine-rich NES in the N terminus of RIP3 that contributes to the cytoplasmic distribution in a CRM1-independent manner. Thus, we provide the first evidence that RIP3 acts a nucleocytoplasmic shuttling protein, which presents a possible link between death receptor signaling and nuclear apoptosis.
Yang
Yonghui
Y
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
Ma
Jun
J
Chen
Youjun
Y
Wu
Mian
M
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
D011494:Protein Kinases; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D007930:Leucine