Journal article
Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond
Post-translational modification of proteins with ubiquitin (ubiquitination) provides a rapid and versatile mechanism for regulating cellular signalling systems. Met1-linked (or 'linear') ubiquitin chains have emerged as a key regulatory signal that controls cell death, immune signalling, and other vital cellular functions.
The molecular machinery that assembles, senses, and disassembles Met1-linked ubiquitin chains is highly specific. In recent years, the thorough biochemical and genetic characterisation of the enzymes and proteins of the Met1-linked ubiquitin signalling machinery has paved the way for substantial advances in our understanding of how Met1-linked ubiquitin chains control cell signalling and biology.
Here, we review current knowledge and recent insights into the role of Met1-linked ubiquitin chains in cell signalling with an emphasis on their role in disease biology. Met1-linked ubiquitin has potent regulatory functions in immune signalling, NF-κB transcription factor activation, and cell death.
Importantly, mounting evidence shows that dysregulation of Met1-linked ubiquitin signalling is associated with multiple human diseases, including immune disorders, cancer, and neurodegeneration. We discuss the latest evidence on the cellular function of Met1-linked ubiquitin in the context of its associated diseases and highlight new emerging roles of Met1-linked ubiquitin chains in cell signalling, including regulation of protein quality control and metabolism.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2021 |
Pages: | 473-492 |
Journal subtitle: | Official Journal of the Admc Associazione Differenziamento E Morte Cellulare |
ISSN: | 14765403 and 13509047 |
Types: | Journal article |
DOI: | 10.1038/s41418-020-00676-w |
ORCIDs: | Elbæk, Camilla Reiter , Damgaard, Rune Busk and Jahan, Akhee Sabiha |