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Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms | SpringerLink
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Injury and growth stimulation both remarkably increase the hepatic expression of Gadd45β. In liver cancer, promoter methylation frequently silences Gadd45β, demonstrating due to a suppressive function that is often proapoptotic. This contrasts with normal...
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Keywords {🔍}
google, scholar, pubmed, article, cas, liver, cell, gadd, growth, expression, jnk, nuclear, receptor, biol, gene, chapter, binding, gaddbeta, transcriptional, gaddβ, regeneration, dna, factor, res, analysis, genes, cancer, proliferation, kinase, arrest, papa, mice, chem, signal, car, hepatocellular, carcinoma, induction, nature, mol, hoffman, beta, privacy, cookies, content, information, publish, stress, mechanisms, tian,
Topics {✒️}
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ScholarlyArticle:
headline:Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms
pageEnd:80
pageStart:69
image:https://media.springernature.com/w153/springer-static/cover/book/978-1-4614-8289-5.jpg
genre:
Biomedical and Life Sciences
Biomedical and Life Sciences (R0)
isPartOf:
name:Gadd45 Stress Sensor Genes
isbn:
978-1-4614-8289-5
978-1-4614-8288-8
type:Book
publisher:
name:Springer New York
logo:
url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
type:ImageObject
type:Organization
author:
name:Jianmin Tian
affiliation:
name:University of Pittsburgh School of Medicine
address:
name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
type:PostalAddress
type:Organization
type:Person
name:Joseph Locker
affiliation:
name:University of Pittsburgh School of Medicine
address:
name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
type:PostalAddress
type:Organization
email:[email protected]
type:Person
keywords:Liver Regeneration, Partial Hepatectomy, Constitutive Androstane Receptor, Transcriptional Mechanism, Gadd45 Protein
description:Injury and growth stimulation both remarkably increase the hepatic expression of Gadd45β. In liver cancer, promoter methylation frequently silences Gadd45β, demonstrating due to a suppressive function that is often proapoptotic. This contrasts with normal hepatocytes, where Gadd45β facilitates cell survival, growth, and proliferation. Gadd45β binds MKK7—downstream of TNFα and its receptors—to prevent this kinase from activating JNK2. Hence, the Gadd45b−/− genotype increases cell injury and decreases cell proliferation during liver regeneration (i.e., compensatory growth and proliferation). Liver hyperplasia (i.e., de novo growth and proliferation) is an alternate form of growth, caused by drugs that activate the nuclear receptor, CAR. As in regeneration, the Gadd45b−/− genotype considerably slows growth during hyperplasia. However, there is no injury and the slowing occurs because Gadd45β normally binds to CAR and activates its transcriptional stimulation. Thus, Gadd45β protects the liver through two entirely different processes: binding MKK7 to block damaging signal transduction or binding CAR to coactivate anabolic transcription.
datePublished:2013
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name:University of Pittsburgh School of Medicine
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type:PostalAddress
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name:Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, USA
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