Anti-Keap1 antibody - C-terminal

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

Keap1 also known as Kelch-like ECH-associated protein 1 plays an important role in regulating the NRF2 protein. Keap1 has a molecular weight of around 70 kDa. It expresses widely throughout mammalian tissues reflecting its significance in cellular functions. As a substrate adaptor protein for the cullin-3-based E3 ubiquitin ligase complex its main function involves the promotion of NRF2 degradation. Keap1 recognizes and binds to specific motifs on NRF2 tagging it for ubiquitination and subsequent proteasomal degradation under homeostatic conditions.

Biological function summary

Keap1 serves as a sensor for oxidative stress within the cell. It constitutes part of a larger biological complex that includes the NRF2 protein and the cullin-3-based E3 ligase complex. In the presence of oxidative or electrophilic stress modifications in Keap1 cysteine thiol groups lead to conformational changes inhibiting Keap1’s ability to target NRF2 for degradation. This results in the accumulation and activation of NRF2 which migrates to the nucleus where it promotes the expression of antioxidant response element (ARE)-driven genes important for cellular defense mechanisms.

Pathways

Keap1 plays a central role in the NRF2-ARE signaling pathway a major player in the antioxidant response of cells. This pathway connects to various processes including detoxification and the regulation of oxidative stress. Keap1 interacts with other proteins such as cullin-3 which is vital for ubiquitin tagging of NRF2. Additionally Keap1 influences the WNT signaling pathway through its interactions with other proteins impacting processes related to cellular proliferation and differentiation.

Associated diseases and disorders

Keap1 relates prominently to certain cancers and neurodegenerative diseases. Mutations or dysregulations in Keap1 or its pathway can lead to abnormal accumulation of NRF2 potentially resulting in enhanced cell survival and proliferation which is characteristic of some cancer types. Moreover Keap1 has been linked to neurodegenerative disorders like Alzheimer's disease where oxidative stress and disrupted NRF2 signaling play contributory roles. Connections within these conditions often involve proteins like NRF2 which interacts closely with Keap1 in the context of pathophysiological cellular responses.