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Amino acid metabolism and disease

When cells are exposed to oxidative stress, electrophiles or chemopreventive agents, Nrf2 escapes Keap1-mediated repression, and translocates and accumulates in the nucleus, thus activating ARE-dependent gene expression to maintain cellular redox homeostasis.174,175 Several mechanisms have been proposed to explain the repressive effect of Keap1 on Nrf2, namely: i) Keap1 is a thiol-rich sensor protein, which is an adaptor protein for Cullin 3-dependent ubiquitination and degradation of Nrf2;176 electrophile modification of the Keap1 central linker domain would switch ubiquitination from Nrf2 to Keap1, leading to Nrf2 activation

Such a combination reveals a therapeutic opportunity for breast cancer

doi: 10.1002/dmrr.1049 85 InceHTademirHAAydinMOzyrekHTilkiHE

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Patients might experience acute attacks, which are characterized by intense pain primarily in the abdomen, along with gastrointestinal symptoms such as nausea, vomiting, and/or constipation