Significance of KEAP1 and NRF2 Protein-Protein Interactions in Cancer

Dear Colleagues,

It is estimated that there are several hundred thousand binary protein–protein interactions in human cells. These interactions govern diverse biological processes, including signaling pathways frequently dysregulated in cancer. One such pathway is the KEAP1–NRF2 axis, which regulates cellular responses to oxidants and electrophiles. Under basal conditions, KEAP1 binds the transcription factor NRF2 and targets it for degradation. In contrast, oxidative or electrophilic stress induces conformational changes in the KEAP1–NRF2 complex that block NRF2 ubiquitination and activate the pathway.

NRF2 plays a dual role in cancer. It protects normal cells from oxidative and electrophilic damage that can lead to mutations and genomic instability—both hallmarks of cancer—thus acting as a suppressor of cancer initiation. However, in established tumors, NRF2 can promote cancer progression by protecting malignant cells from oxidative stress, enabling the detoxification of chemotherapeutics, supporting metabolic reprogramming, and suppressing antitumor immunity. Consequently, NRF2 is frequently constitutively activated in several cancer types.

Multiple mechanisms contribute to NRF2 overexpression in cancer. One of these involves the overexpression of proteins that competitively interact with KEAP1 or NRF2, thereby inhibiting NRF2 ubiquitination and degradation.

For this Special Issue, we welcome submissions addressing KEAP1, NRF2, and their interactions, with an emphasis on their roles in cancers.

Dr. Mihaela Matovina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.