ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease

Abstract

Summary 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.

Thermal Bioprinting Causes Ample Alterations of Expression of LUCAT1, IL6, CCL26, and NRN1L Genes and Massive Phosphorylation of Critical Oncogenic Drug Resistance Pathways in Breast Cancer Cells

“…Mitogen Activated Protein Kinase Kinase 6 (AP2K6 or MKK6) has a critical role in the MAPK signal transduction pathway (Raingeaud et al, 1996), as it can activate p38 (Moriguchi et al, 1996;Raingeaud et al, 1996;Stein et al, 1996) in which then leads toward the specific activation of transcription factors, such as activating transcription factor 2 (ATF2) and ETS-like 1 (Elk1) (Goedert et al, 1997). ATF2 dysfunction has been linked to cancer metastasis (Watson et al, 2017) These proteins are activated by several insults, such as heat shock, UV rays, osmotic shock, cellular DNA damage and their regulation remains obscure (Goedert et al, 1997). The phosphorylation level of MKK6/MKK3 was observed in the BP cells yet it was not seen in the MS MCF7 cells.…”

6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis

“…ATF2 is a member of the CREB/ATF transcription factor family, and members possess a leucine zipper domain [38]. These proteins contribute to various cell behaviours, including regulating cell development, proliferation and cell death, as well as cellular responses to stress signals and DNA damage [39,40]. Evidence suggests that ATF2 is imbalanced in individuals with cancer, whereas complete loss of ATF2 in somatic cells leads to cell death [39,41,42].…”

LncRNAs in HCV Infection and HCV-Related Liver Disease

“…After transcription, hnRNPU (heterogeneous nuclear ribonucleoprotein U) binds to and stabilizes LUARIS. In addition, LUARIS interacts with ATF2 (activating transcription factor 2), a transcription factor that regulates the expression of several genes, including those involved in anti-apoptosis, DNA damage response, cell growth, and inflammation [95,96]. Binding to LUARIS is required for ATF2 interaction to a cAMP-responsive element located in the intron of IRF7 and IFN-independent ISG expression.…”