Abstract
The transcription factor FOSL1 plays an important role in cell differentiation and tumorigenesis. Primarily, FOSL1 is crucial for the differentiation of several cell lineages, namely adipocytes, chondrocytes, and osteoblasts. In solid tumors, FOSL1 controls the progression of tumor cells through the epithelial–mesenchymal transformation. In this review, we summarize the available data on FOSL1 expression, stabilization, and degradation in the cell. We discuss how FOSL1 is integrated into the intracellular signaling mechanisms and provide a comprehensive analysis of FOSL1 influence on gene expression. We also analyze the pathological changes caused by altered Fosl1 expression in genetically modified mice. In addition, we dedicated a separate section of the review to the role of FOSL1 in human cancer. Primarily, we focus on the FOSL1 expression pattern in solid tumors, FOSL1 importance as a prognostic factor, and FOSL1 perspectives as a molecular target for anticancer therapy.
Highlights
FOSL1 protein is often considered a subunit of the transcriptional complex AP1
This review aimed to summarize the available data on the role of the transcription factor FOSL1 in the regulation of gene expression, its contribution to the intracellular signaling mechanisms, and evaluate its clinical value as a molecular target and prognostic factor for anticancer therapy
Unlike Fosl1 overexpressing cells, Fosl1-silenced cells suppress the genes associated with the mesenchymal phenotype, including the epithelial-mesenchymal transition (EMT) promoting transcription factors Snail, Slug/Snai2, Zeb1, and Zeb2, and induce the genes expressed by the epithelial cells (e.g., Cdh1) [6]
Summary
FOSL1 protein is often considered a subunit of the transcriptional complex AP1. It plays a crucial role in cell differentiation, response to environmental stresses, and tumorigenesis. Since different signaling pathways activate AP1 and CREB and rotating the transcription factor at the binding site allows the cell to tune up the transcription, this crosstalk has to regulate the gene expression. FOSL1 heterodimerizes with other transcription factors, such as the members of the bZIP family Their hybrid heterodimers (e.g., FOSL1-USF2 [4,5]) can be transcriptionally inactive. Their possible role in the cell may include but not be limited to sequestering FOSL1 in the nucleus These dimers are either disabling the transcriptional activator complex or saving the interacting proteins from degradation in proteasomes. The interaction FOSL1 with different binding partners would allow the cell to control the transcription of more genes with fewer numbers of specialized proteins
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