An essential role in liver development for transcription factor XBP-1

AM Reimold, A Etkin, I Clauss, A Perkins… - Genes & …, 2000 - genesdev.cshlp.org
AM Reimold, A Etkin, I Clauss, A Perkins, DS Friend, J Zhang, HF Horton, A Scott, SH Orkin
Genes & development, 2000genesdev.cshlp.org
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 …
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 αFP, 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.
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