Ubiquitination is a protein post-translational modification that affects protein localisation, stability and interactions. E3 ubiquitin ligases regulate the final step of the ubiquitination reaction by recognising target proteins and mediating the ubiquitin transfer from an E2 enzyme. DTX3L is a multi-domain E3 ubiquitin ligase in which the N-terminus mediates protein oligomerisation, a middle D3 domain mediates the interaction with PARP9, a RING domain responsible for recognising E2 ∼ Ub and a DTC domain has the dual activity of ADP-ribosylating ubiquitin and mediating ubiquitination. The activity of DTX3L is known to be modulated by at least two different factors: the concentration of NAD+, which dictates if the enzyme acts as a ligase or as an ADP-ribosyltransferase, and its binding partners, which affect DTX3L activity through yet unknown mechanisms. In light of recent findings it is possible that DTX3L could ubiquitinate ADP-ribose attached to proteins. Different DTX3L–protein complexes have been found to be part of multiple signalling pathways through which they promote the adhesion, proliferation, migration and chemoresistance of e.g. lymphoma, glioma, melanoma, and prostate cancer. In this review, we have covered the literature available for the molecular functions of DTX3L especially in the context of cancer biology, different pathways it regulates and how these relate to its function as an oncoprotein.
Many dietary plants possess high levels of 18-carbon containing lipids from both omega-6 and omega-3 unsaturated fatty acids (e.g., linoleic and alpha-linolenic acid, respectively). These dietary lipids can be metabolized to lipid mediators collectively termed octadecanoids, which can in turn interact with immune cells (e.g., macrophages, eosinophils) to exert a number of potent biological effects. These octadecanoid lipid mediators have been little studied and represent an exciting new area of lipid biochemistry. For further information, see the review in this issue by Quaranta and colleagues (pages 1569–1582). Cover image credit: Emmanuelle Chevallier.
Activities and binding partners of E3 ubiquitin ligase DTX3L and its roles in cancer
Carlos Vela-Rodríguez, Lari Lehtiö; Activities and binding partners of E3 ubiquitin ligase DTX3L and its roles in cancer. Biochem Soc Trans 16 December 2022; 50 (6): 1683–1692. doi: https://doi.org/10.1042/BST20220501
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