Nature Reviews Molecular Cell Biology, Published online: 14 July 2025; doi:10.1038/s41580-025-00870-zDegrons allow E3 ubiquitin ligases to identify their substrates, and thus have a central role in protein degradation by the ubiquitin–proteasome system. This Review discusses the latest insights into the mechanisms underlying degron function, the relevance of degrons in disease and how degrons can be harnessed for therapeutic protein degradation.

In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

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We find that when disseminated breast cancer cells enter the lung, embryo-derived alveolar macrophages (AMs) serve as an innate immune barrier to metastasis. This occurs because AMs produce signals that induce dormancy in the cancer cells. As cancer evolves, cancer cells eliminate their ability to sense the AM-derived pro-dormancy signals, developing a mechanism of resistance to this AM-dependent innate immune control of metastasis.