A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation.
Receptor-interacting protein (RIP) is a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation. In a yeast two-hybrid screening for potential RIP-interacting proteins, we identified ZIN (zinc finger protein inhibiting NF-kappa B), a novel protein that specifically interacts with RIP. ZIN contains four RING-like zinc finger domains at the middle and a proline-rich domain at the C terminus. Overexpression of ZIN inhibits RIP-, IKK beta-, TNF-, and IL1-induced NF-kappa B activation in a dose-dependent manner in 293 cells. Domain mapping experiments indicate that the RING-like zinc finger domains of ZIN are required for its interaction with RIP and inhibition of RIP-mediated NF-kappa B activation. Overexpression of ZIN also potentiates RIP- and TNF-induced apoptosis. Moreover, immunofluorescent staining indicates that ZIN is a cytoplasmic protein and that it colocalizes with RIP. Our findings suggest that ZIN is an inhibitor of TNF- and IL1-induced NF-kappa B activation pathways.
Chen
Danying
D
Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China.
Li
Xiaoyan
X
Zhai
Zhonghe
Z
Shu
Hong-Bing
HB
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
D002352:Carrier Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C458527:RNF216 protein, human; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases