Structural and Functional Properties of Activator Protein-1 in Cancer and Inflammation

Abstract

The transcriptional machinery is composed of numerous factors that help to regulate gene expression in cells. The function and the fundamental role of transcription factors in different human diseases and cancer have been extensively researched. Activator protein-1 (AP-1) is an inducible transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and survival in cells. Dysfunctional AP-1 activity is seen in several diseases, especially cancer and inflammatory disorders. The AP-1 proteins are controlled by mitogen-activated protein kinases (MAPKs) and the NF-κB pathway. AP-1 inhibitors can be actively pursued as drug discovery targets in cancer therapy when used as a treatment to halt tumor progression. The consumption of phytochemicals in the diet is related to decreasing the incidence of cancer and proves to exhibit anticancer properties. Natural product targets AP-1 are effective cancer prevention and treatment options for various cancer types. Targeting AP-1 with natural products is an effective cancer treatment option for different cancer types. This review summarizes AP-1 subunit proteins, their structures, AP-1-related signaling, and its modulation by natural bioactive compounds.

Figure 1

Structure of activator protein (AP)-1. The carboxy-terminal regions of α-helixes align to form parallel “coiled coils”, while the amino-terminal regions make base-specific contacts with DNA in the major groove (PDB code 1Fos). Coils forming leucine zipper in blue and pink are c-Fos and c-Jun, respectively.

Figure 2

Illustration of the NF-κB pathway in AP-1. NF-κB is an inducible transcription factor that activates various genes and thereby regulates the inflammatory process.

Figure 3

MAPK- and AP-1-related signaling pathways. MAPK signaling integrates signals from diverse stimuli and elicits appropriate responses such as cellular proliferation, development, apoptosis, and inflammatory responses in cells. Schematic representation of MAPK and AP-1 pathways explained in the text.

Figure 4

Schematic representation of AP-1 in cancer. AP-1 transcription factor regulates gene expression in response to various stimuli and controls the number of cellular processes in cells.