AP-1/c-Jun transcription factors: regulation and function in malignant melanoma

Abstract

Malignant melanoma is an aggressive form of skin cancer with an increasing incidence worldwide. One way to address the pathology of the disease is through molecular research. In addition to the analysis of melanoma-relevant signaling pathways, the investigation of important transcription factors is a fundamental objective. The AP-1 transcription factor family is known to play an important role in melanoma progression and development. The AP-1 family member c-Jun is highly expressed and active in melanoma cells, and the mechanisms and signaling pathways regulating c-Jun protein are diverse. In addition to the common regulation and activation of c-Jun by mitogen-activated protein kinases (MAPKs), there are several other signaling pathways and interactions leading to c-Jun protein expression and thus AP-1 activation. In malignant melanoma, and many other cancer types, c-Jun has mainly oncogenic functions; however, other AP-1 proteins also have anti-oncogenic roles. Interestingly, several studies have revealed that a strong AP-1 activity in melanoma mainly depends on c-Jun. Recently, it has also been shown that the c-Jun protein is regulated and activated by several other mechanisms, including miRNAs and the cytoskeleton. In summary, there are a variety of mechanisms underlying the induction of c-Jun protein expression and activity leading to tumor progression and development, and this diverse regulatory machinery is due to the heterogeneity of different tumor types, particularly in malignant melanoma.

Keywords: AP-1; Cytoskeleton; Melanoma; Post-transcriptional regulation; c-Jun; miR.