DTX3L
Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value).
Deltex E3 ubiquitin ligase 3L is a protein that in humans is encoded by the DTX3L gene.[1] It functions as an ubiquitin ligase (E3),[2] and is over-expressed in chemotherapy-resistant lymphomas.[3] It is a member of the DTX family of proteins.[4] Among other roles it has a function in DNA damage repair.
It was discovered through two-hybrid screening during a search for binding partners of PARP9 (formerly BAL[5]), a gene related to the risk of B-cell lymphoma. and was originally named BBAP (B-lymphoma- and BAL-associated protein).[2]
DTX3L and PARP9 are both located in the same 48kB region of the genome, and are both regulated by a IFN-γ-responsive bidirectional promoter.[6] DTX3L has a long N-terminus domain distinct from other DTX-family proteins that allows it form dimers with itself and other proteins.[4] It has been found to be up-regulated by METTL3.[4]
Function
[edit | edit source]DTX3L functions as an ubiquitin ligase or E3.[2] These proteins bind to ubiquitin-conjugating enzymes (E2s), and then transfer and bind the ubiquitin (activated by E1s) from the E2s to the target protein.[7] Along with all other known DTX-family proteins (as of 2023), DTX3L is involved in the regulation of Notch signaling.[4]
DTX3L also plays a role in DNA damage repair,[4] which has been associated with its ability to selectively mono-ubiquitylate (bind one ubiquitin to) histone H4.[3][4] It helps to protect cells exposed to DNA damaging agents.[3]
DTX3L can form a complex with PARP9.[8] This complex functions as a ubiquitin ligase and ubiquitinates both host histone H2BJ, to promote expression of interferon-stimulated genes, and viral 3C protease to disrupt viral assembly.[8] This can help to control viral infection.[8] PARP9 can also affect DXT3L's function in DNA damage repair.[4] The DXT3L-PARP9 complex mediates mono-ADP-ribosylation of ubiquitin; this prevents it from being conjugated[9] and inhibits DXT3L's function as an ubiquitin ligase.[4] The NAD+ dependent binding of PARP9 to poly-ADP-ribose, instead, enhances the activity of DXT3L as a ubiquitin ligase.[4][why?] DTX3L can also form a complex with DTX1.[4]
DTX3L also affects signaling by inhibiting the sorting of the G-protein coupled receptor CXCR4 through the endosomes to degradation in the lysosomes.[10] When CXCR4 is activated, DXT3L localizes to early endosomes and inhibits the E3 ubiquitin ligase atrophin-1 interacting protein 4.[10] This reduces the extent to which the protein ESCRT-0 is ubiquitinated, which reduces its ability to sort CXCR4 into the lysosomes.[10] The implications of this effect (as of 2023) in cancer biology are unknown.[4]
References
[edit | edit source]- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c d e f g h i j k Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
Further reading
[edit | edit source]- Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
