Abstract
The proto-oncogene c-Jun plays essential roles in various cellular processes, including cell proliferation, cell differentiation, and cellular apoptosis. Enormous efforts have been made to understand the mechanisms regulating c-Jun activation. The males absent on the first (MOF)-containing non-specific lethal (NSL) complex has been shown to positively regulate gene expression. However, the biological function of the NSL complex is largely unknown. Here we present evidence showing that c-Jun recruits the NSL complex to c-Jun target genes upon activation. The NSL complex catalyzes H4K16 acetylation at c-Jun target genes, thereby promoting c-Jun target gene transcription. More interestingly, we also found that the NSL complex promotes the release of the repressive NuRD complex from c-Jun target genes, thus activating c-Jun. Our findings not only reveal a new mechanism regulating c-Jun activation, but also identify the NSL complex as a c-Jun co-activator in c-Jun-regulated gene expression, expanding our knowledge of the function of the NSL complex in gene expression regulation.
Highlights
C-Jun, the major AP-1 transcription factor family member, is activated by a broad range of extracellular signals, including growth factors, cytokines and extracellular stresses [1]
In mitogen activated protein kinase (MAPK) signaling pathways, the downstream transcription factor c-Jun is activated by Jun N-terminal kinase (JNK)-mediated phosphorylation in response to a variety of extracellular stimuli
C-Jun phosphorylation promotes its release from the repressive Nucleosome Remodeling Deacetylase (NuRD) complex
Summary
C-Jun, the major AP-1 transcription factor family member, is activated by a broad range of extracellular signals, including growth factors, cytokines and extracellular stresses [1]. C-Jun plays essential roles in a variety of cellular processes, ranging from cell proliferation and differentiation to tumorigenesis and cellular apoptosis [2,3,4,5]. C-Jun has been shown to be essential in the development of skin and liver tumors [14, 15]. Several studies have demonstrated that c-Jun possesses the potential to induce malignant transformation of several cell lines [16, 17]. C-Jun exerts its regulatory role in cellular proliferation and transformation by regulating proliferation-stimulating genes, such as EGFR, KGF, CyclinD1, and CDC2 [18,19,20,21]. C-Jun downregulates the tumor suppressor gene p53 to inhibit apoptosis [22, 23]. C-Jun enhances angiogenesis and invasiveness by regulating Proliferin and CD44 respectively [24, 25]
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