title: ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease.
abstract: Stringent transcriptional regulation is crucial for normal cellular biology and organismal development. Perturbations in the proper regulation of transcription factors can result in numerous pathologies, including cancer. Thus, understanding how transcription factors are regulated and how they are dysregulated in disease states is key to the therapeutic targeting of these factors and/or the pathways that they regulate. Activating transcription factor 2 (ATF2) has been studied in a number of developmental and pathological conditions. Recent findings have shed light on the transcriptional, post-transcriptional, and post-translational regulatory mechanisms that influence ATF2 function, and thus, the transcriptional programs coordinated by ATF2. Given our current knowledge of its multiple levels of regulation and function, ATF2 represents a paradigm for the mechanistic complexity that can regulate transcription factor function. Thus, increasing our understanding of the regulation and function of ATF2 will provide insights into fundamental regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into a genomic response through transcription factors. Characterization of ATF2 dysfunction in the context of pathological conditions, particularly in cancer biology and response to therapy, will be important in understanding how pathways controlled by ATF2 or other transcription factors might be therapeutically exploited. In this review, we provide an overview of the currently known upstream regulators and downstream targets of ATF2.
authors.affiliation: Department of Tumor Biology and Program in Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Watson
authors.affiliation: Tumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, 3109601, Israel.
authors.forename: Ze'ev A
authors.initials: ZA
authors.lastname: Ronai
authors.affiliation: Department of Tumor Biology and Program in Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center, Tampa, FL, USA. Electronic address: Eric.Lau@Moffitt.org.
authors.forename: Eric
authors.initials: E
authors.lastname: Lau
mesh_terms: D051698:Activating Transcription Factor 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D055808:Drug Discovery; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2
keywords: Activating Transcription Factor 2 (ATF2); Activator Protein 1 (AP1); Cancer; Signal transduction; Transcription factor