[Functional analysis of apoptosis signal-regulating kinase 1 (ASK 1)-binding proteins].
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are pleiotropic cytokines that activate two transcription factors, Activator Protein-1 (AP-1) and Nuclear Factor-kappa B (NF-kappa B). Apoptosis signal-regulating kinase 1 (ASK 1) is a mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK) that is activated by TNF and IL-1, and stimulates c-Jun N-terminal kinase (JNK also known as SAPK; stress-activated protein kinase) and p38 activation. Through genetic screening for ASK 1-binding proteins, Transforming Growth Factor beta (TGF-beta)-activated kinase (TAK 1), another MAPKKK family protein, was identified. Here we report that ASK 1 binds to TAK 1 and dissociates TAK 1 from TNF receptor-associated factor 6 (TRAF 6), and inhibits TAK 1- and TRAF 6-, but not NF-kappa B-inducing kinase (NIK)-induced NF-kappa B activation.
Mochida
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Division of Maxillofacial and Neck Reconstruction, Graduate School, Tokyo Medical and Dental University.
D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C482858:MAP3K5 protein, human