TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members.
The TRIM family of proteins is distinguished by its tripartite motif (TRIM). Typically, TRIM proteins contain a RING finger domain, one or two B-box domains, a coiled-coil domain and the more variable C-terminal domains. TRIM16 does not have a RING domain but does harbour two B-box domains. Here we showed that TRIM16 homodimerized through its coiled-coil domain and heterodimerized with other TRIM family members; TRIM24, Promyelocytic leukaemia (PML) protein and Midline-1 (MID1). Although, TRIM16 has no classic RING domain, three-dimensional modelling of TRIM16 suggested that its B-box domains adopts RING-like folds leading to the hypothesis that TRIM16 acts as an ubiquitin ligase. Consistent with this hypothesis, we demonstrated that TRIM16, devoid of a classical RING domain had auto-polyubiquitination activity and acted as an E3 ubiquitin ligase in vivo and in vitro assays. Thus via its unique structure, TRIM16 possesses both heterodimerization function with other TRIM proteins and also has E3 ubiquitin ligase activity.
Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Randwick, New South Wales, Australia.
Jessica L
JL
Bell
Alena
A
Malyukova
Jessica K
JK
Holien
Jessica
J
Koach
Michael W
MW
Parker
Maria
M
Kavallaris
Glenn M
GM
Marshall
Belamy B
BB
Cheung
D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D004268:DNA-Binding Proteins; D008868:Microtubule Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C109052:MID1 protein, human; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases