Ubiquitination (K48 vs. K63 Linkages)

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signaling-pathways

Ubiquitination is a post-translational modification in which the small protein ubiquitin is covalently attached to lysine residues of a substrate protein, often as chains of multiple ubiquitin molecules linked through one of several internal lysines. K48-linked polyubiquitin chains are the classical signal for proteasomal degradation of the tagged protein, whereas K63-linked chains typically serve non-degradative signaling roles such as protein trafficking, complex assembly, or activation of downstream signaling cascades. E3 ubiquitin ligases such as Parkin can select different linkage types depending on the substrate and the intended biological outcome.

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Source papers

  • Parkin Ubiquitination of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C. Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M. Cecilia Caino, Dario C. Altieri · 2023 doi:10.1016/j.jbc.2023.104774
  • Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity Minjeong Yeon, Michela Perego, Khaled M. Elokely, Magid Abou-Gharbia, Wayne E. Childers, Andrew T. Milcarek, Irene Bertolini, Hsin-Yao Tang, Lucia R. Languino, Gary S. Stein, Prachi N. Ghule, Brad P. Vietje, Douglas T. Taatjes, Dario C. Altieri · 2025 doi:10.1158/0008-5472.CAN-25-0904