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- Title
LIGHT induces differentiation of mouse embryonic stem cells associated with activation of ERK5.
- Authors
Zou, G. -M.; Chen, J. -J.; Ni, J.
- Abstract
LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) is a recently cloned type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively defined in its role on T-cell regulation and dendritic cell maturation. However, whether this cytokine regulates stem cell proliferation and/or differentiation remains unknown. In this study, we transduced exogenous LIGHT into embryonic stem cells (ES cells) and found it induced their differentiation. The expression of phospho-STAT3, Nanog and Oct-4 was reduced in LIGHT-transduced ES cells compared with wild-type ES cells. LIGHT-transduced ES cells exhibit a low level of SSEA-1 surface antigen and alkaline phosphatase staining compared with wild-type cells. Introduction of LIGHT into ES cells results in the dephosphorylation of MKP-3 and activation of extracellular signal-regulated kinase (ERK)5. When ERK5 was inhibited by the specific inhibitor PD184352 or knocked down by ERK5 siRNA, reduction of Oct-4 and SSEA-1 expression was rescued. We conclude that LIGHT overrides Leukemia inhibitory factor to induce ES cell differentiation associated with activation of ERK5.Oncogene (2006) 25, 463–469. doi:10.1038/sj.onc.1208987; published online 10 October 2005
- Subjects
LIGANDS (Biochemistry); EMBRYONIC stem cells; GLYCOPROTEINS; T cells; APOPTOSIS; LEUKEMIA inhibitory factor
- Publication
Oncogene, 2006, Vol 25, Issue 3, p463
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208987