Journal article
Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response
Cell, Vol.124(3), pp.587-599
2006
DOI: 10.1016/j.cell.2005.11.040
PMID: 16469704
Abstract
Regulated intramembrane proteolysis (RIP) of endoplasmic reticulum (ER) membrane-anchored transcription factors is known to maintain sterol homeostasis and to mediate the unfolded protein response (UPR). Here, we identified CREBH as a RIP-regulated liver-specific transcription factor that is cleaved upon ER stress and required to activate expression of acute phase response (APR) genes. Proinflammatory cytokines increase expression of ER membrane-anchored CREBH. In response to ER stress, CREBH is cleaved by site-1 and site-2 proteases to liberate an amino-terminal fragment that transits to the nucleus to activate transcription of the genes encoding serum amyloid P-component (SAP) and C-reactive protein (CRP). Proinflammatory cytokines and lipopolysaccharide activate the UPR and induce cleavage of CREBH in the liver in vivo. Together, our studies delineate a molecular mechanism for activation of an ER-localized transcription factor, CREBH, and reveal an unprecedented link by which ER stress initiates an acute inflammatory response.
Details
- Title: Subtitle
- Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response
- Creators
- Kezhong Zhang - Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USAXiaohua Shen - Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USAJun Wu - Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USAKenjiro Sakaki - Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USAThomas Saunders - Transgenic Animal Model Core, University of Michigan Medical Center, Ann Arbor, MI 48109, USAD. Thomas Rutkowski - Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USASung Hoon Back - Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USARandal J Kaufman - Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.124(3), pp.587-599
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2005.11.040
- PMID
- 16469704
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2006
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984094322602771
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