An essential role in liver development for transcription factor 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 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.
Reimold
A M
AM
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115 USA.
Etkin
A
A
Clauss
I
I
Perkins
A
A
Friend
D S
DS
Zhang
J
J
Horton
H F
HF
Scott
A
A
Orkin
S H
SH
Byrne
M C
MC
Grusby
M J
MJ
Glimcher
L H
LH
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000235:genetics; D018390:Gene Targeting; D005804:Genes, Lethal / Q000235:genetics; D006498:Hepatectomy; D008099:Liver / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071701:Regulatory Factor X Transcription Factors; D013234:Stem Cells; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse