Abstract
TGF-β-activated kinase 1 (TAK1 or MAP3K7) is an intracellular hub molecule that regulates both nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that play key roles in development, cell survival, immune response, metabolism, and carcinogenesis. TAK1 activity is tightly regulated by its binding proteins, TAB1 and TAB2/TAB3, as well as by post-translational modification including ubiquitination and phosphorylation. Accumulating evidence demonstrates that TAK1 plays a role in tumor initiation, progression, and metastasis as a tumor prompter or tumor suppressor. An understanding of the role of TAK1 in liver physiology and diseases is required for the development of therapeutic agencies targeting TAK1. In this review, we highlight the activation mechanism and pathophysiological roles of TAK1 in the liver.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Survival
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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DNA Repair
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Hepatocytes / enzymology*
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Liver Neoplasms / drug therapy
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Liver Neoplasms / enzymology*
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MAP Kinase Kinase Kinases / genetics
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MAP Kinase Kinase Kinases / metabolism
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MAP Kinase Kinase Kinases / physiology*
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MAP Kinase Signaling System*
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Molecular Targeted Therapy
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NF-kappa B / metabolism
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Transforming Growth Factor beta / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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TAB1 protein, human
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TAB2 protein, human
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TAB3 protein, human
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Transforming Growth Factor beta
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7