AI Article Synopsis
- C/EBP-beta is a transcription factor that plays a key role in regulating gene expression in response to external signals, specifically through an element activated by interferon-gamma (IFN-gamma).
- The study highlights that mixed lineage kinases (MLKs), particularly MLK3, are essential for the regulation of C/EBP-beta when activated by IFN-gamma, primarily by altering the phosphorylation of a specific residue.
- This research reveals a new mechanism of how IFN-gamma can activate transcription, underscoring MLK3's importance in the signaling pathway linked to immune responses.
Article Abstract
Transcription factor CCAAT/enhancer-binding protein-beta (C/EBP-beta) regulates a variety of cellular functions in response to exogenous stimuli. We have reported earlier that C/EBP-beta induces gene transcription through a novel interferon (IFN)-response element called gamma-IFN-activated transcriptional element. We show here that IFN-gamma-induced, C/EBP-beta/gamma-IFN-activated transcriptional element-dependent gene expression is regulated by mixed lineage kinases (MLKs), members of the mitogen-activated protein kinase kinase kinase family. MLK3 appears to activate C/EBP-beta in response to IFN-gamma by a mechanism involving decreased phosphorylation of a specific phosphoacceptor residue, Ser(64), within the transactivation domain. Decreased phosphorylation of Ser(64) was independent of IFN-gamma-stimulated ERK1/2 activation and did not require the ERK phosphorylation site Thr(189) located in regulatory domain 2 of C/EBP-beta. Together these studies provide the first evidence that MLK3 is involved in IFN-gamma signaling and identify a novel mechanism of transcriptional activation by IFN-gamma.
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| http://dx.doi.org/10.1074/jbc.M413661200 | DOI Listing |
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