Beyond repression of Nrf2: An update on Keap1.

Nrf2 (NFE2L2 – nuclear factor (erythroid-derived 2)-like 2) is a transcription factor, which is repressed by interaction with a redox-sensitive protein Keap1 (Kelch-like ECH-associated protein 1). Deregulation of Nrf2 transcriptional activity has been described in the pathogenesis of multiple diseases, and the Nrf2/Keap1 axis has emerged as a crucial modulator of cellular homeostasis. Whereas the significance of Nrf2 in the modulation of biological processes has been well established and broadly discussed in detail, the focus on Keap1 rarely goes beyond the regulation of Nrf2 activity and redox sensing. However, recent studies and scrutinized analysis of available data point to Keap1 as an intriguing and potent regulator of cellular function. This review aims to shed more light on Keap1 structure, interactome, regulation and non-canonical functions, thereby enhancing its significance in cell biology. We also intend to highlight the impact of balance between Keap1 and Nrf2 in the maintenance of cellular homeostasis. Image 1 • In this review we emphasize the non-canonical functions of Keap1. • We summarize numerous post-translational modifications on Keap1 and its rich interactome. • The modes of Keap1 regulation are presented. • The impact of balance between Keap1 and Nrf2 in the maintenance of cellular homeostasis is highlighted. [ABSTRACT FROM AUTHOR]