Gadd45 in the Liver Signal Transduction and Trans

Authors: Jianmin Tian Joseph Locker

Publish Date: 2013

Volume: , Issue: , Pages: 69-80

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Abstract

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 ie compensatory growth and proliferation Liver hyperplasia ie 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

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