Irod/Ian5: an inhibitor of gamma-radiation- and okadaic acid-induced apoptosis.
Protein phosphatase-directed toxins such as okadaic acid (OA) are general apoptosis inducers. We show that a protein (inhibitor of radiation- and OA-induced apoptosis, Irod/Ian5), belonging to the family of immune-associated nucleotide binding proteins, protected Jurkat T-cells against OA- and gamma-radiation-induced apoptosis. Unlike previously described antiapoptotic proteins Irod/Ian5 did not protect against anti-Fas, tumor necrosis factor-alpha, staurosporine, UV-light, or a number of chemotherapeutic drugs. Irod antagonized a calmodulin-dependent protein kinase II-dependent step upstream of activation of caspase 3. Irod has predicted GTP-binding, coiled-coil, and membrane binding domains. Irod localized to the centrosomal/Golgi/endoplasmic reticulum compartment. Deletion of either the C-terminal membrane binding domain or the N-terminal GTP-binding domain did not affect the antiapoptotic function of Irod, nor the centrosomal localization. The middle part of Irod, containing the coiled-coil domain, was therefore responsible for centrosomal anchoring and resistance toward death. Being widely expressed and able to protect also nonimmune cells, the function of Irod may not be limited to the immune system. The function and localization of Irod indicate that the centrosome and calmodulin-dependent protein kinase II may have important roles in apoptosis signaling.
Sandal
Tone
T
Department of Anatomy and Cell Biology, Medical faculty, University of Bergen, N-5009 Bergen, Norway.
Aumo
Linda
L
Hedin
Lars
L
Gjertsen
Bjørn T
BT
Døskeland
Stein O
SO
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D005720:Gamma Rays; D015723:Gene Library; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009154:Mutation; D019319:Okadaic Acid / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
D004791:Enzyme Inhibitors; C484030:GIMAP5 protein, human; D019319:Okadaic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020169:Caspases; D019204:GTP-Binding Proteins