title: c-Jun, at the crossroad of the signaling network.
abstract: c-Jun, the most extensively studied protein of the activator protein-1 (AP-1) complex, is involved in numerous cell activities, such as proliferation, apoptosis, survival, tumorigenesis and tissue morphogenesis. Earlier studies focused on the structure and function have led to the identification of c-Jun as a basic leucine zipper (bZIP) transcription factor that acts as homo- or heterodimer, binding to DNA and regulating gene transcription. Later on, it was shown that extracellular signals can induce post-translational modifications of c-Jun, resulting in altered transcriptional activity and target gene expression. More recent work has uncovered multiple layers of a complex regulatory scheme in which c-Jun is able to crosstalk, amplify and integrate different signals for tissue development and disease. One example of such scheme is the autocrine amplification loop, in which signal-induced AP-1 activates the c-Jun gene promoter, while increased c-Jun expression feedbacks to potentiate AP-1 activity. Another example of such scheme, based on recent characterization of gene knockout mice, is that c-Jun integrates signals of several developmental pathways, including EGFR-ERK, EGFR-RhoA-ROCK, and activin B-MAP3K1-JNK for embryonic eyelid closure. After more than two decades of extensive research, c-Jun remains at the center stage of a molecular network with mysterious functional properties, some of which are yet to be discovered. In this article, we will provide a brief historical overview of studies on c-Jun regulation and function, and use eyelid development as an example to illustrate the complexity of c-Jun crosstalking with signaling pathways.
authors.affiliation: Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Qinghang
authors.initials: Q
authors.lastname: Meng
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016755:Proto-Oncogene Proteins c-jun