An essential role in liver development for transcription factor XBP-1
Andreas M. Reimold,Amit Etkin,Isabelle M. Clauss,Andrew C. Perkins,Daniel S. Friend,John Zhang,Heidi F. Horton,Andrew R. Scott,Stuart H. Orkin,Michael C. Byrne,Michael J. Grusby,Laurie H. Glimcher +11 more
TLDR
XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas that is essential for liver growth and 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.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 aFP, 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.read more
Citations
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XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor
TL;DR: The transcription factor XBP1, a target of ATF6, is identified as a mammalian substrate of such an unconventional mRNA splicing system and it is shown that only the spliced form of X BP1 can activate the UPR efficiently.
Journal ArticleDOI
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Umut Ozcan,Qiong Cao,Erkan Yilmaz,Ann-Hwee Lee,Neal N. Iwakoshi,Esra Özdelen,Gurol Tuncman,Cem Z. Görgün,Laurie H. Glimcher,Gökhan S. Hotamisligil +9 more
TL;DR: It is shown that obesity causes endoplasmic reticulum (ER) stress, which leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptors substrate–1 (IRS-1).
Journal ArticleDOI
The unfolded protein response: controlling cell fate decisions under ER stress and beyond
TL;DR: Insight is provided into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6).
Journal ArticleDOI
Roles of CHOP/GADD153 in endoplasmic reticulum stress.
TL;DR: The current understanding of the roles of C/EBP homologous protein (CHOP) and GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease are summarized.
Journal ArticleDOI
XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response
TL;DR: It is suggested that the IRE1/XBP-1 pathway is required for efficient protein folding, maturation, and degradation in the ER and imply the existence of subsets of UPR target genes as defined by their dependence on XBP- 1.
References
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Journal ArticleDOI
Scatter factor/hepatocyte growth factor is essential for liver development
C Schmidt,Friedhelm Bladt,S Goedecke,Volker Brinkmann,W Zschiesche,M Sharpe,Ermanno Gherardi,Carmen Birchmeier +7 more
TL;DR: It is reported that mice lacking SF/HGF fail to complete development and die in utero, and the mutation affects the embryonic liver, which is reduced in size and shows extensive loss of parenchymal cells.
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Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis.
Eva Y.-H. P. Lee,Chi-Yao Chang,Nanpin Hu,Yi-Chun J. Wang,Chen-Ching Lai,Karl Herrup,Wen-Hwa Lee,Allan Bradley +7 more
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