Abstract
XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas. Here we report that XBP-1 is essential for liver growth. Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia. Nevertheless, XBP-1-deficient hematopoietic progenitors had no cell-autonomous defect in differentiation. Rather, hepatocyte development itself was severely impaired by two measures: diminished growth rate and prominent apoptosis. Specific target genes of XBP-1 in the liver were identified as alphaFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members. Therefore, XBP-1 is a transcription factor essential for hepatocyte growth.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Embryonic and Fetal Development / genetics
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Gene Targeting
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Genes, Lethal / genetics
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Hepatectomy
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Liver / abnormalities
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Liver / embryology*
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Liver / metabolism
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Mice
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Mice, Knockout
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Regulatory Factor X Transcription Factors
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Stem Cells
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Transcription Factors / biosynthesis
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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X-Box Binding Protein 1
Substances
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DNA-Binding Proteins
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse