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Updated: Aug 18, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
A role for mixed lineage kinases in regulating transcription factor CCAAT/enhancer-binding protein-{beta}-dependent
Sanjit K Roy1, Jon D Shuman, Leonidas C Platanias
1Greenebaum Cancer Center, Department of Microbiology and Immunology, University of Maryland School of Medicine, Balltimore, MD 21201, USA.
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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