The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35.

Autor: Zanchetta ME; Department of Life Sciences, University of Trieste, Italy; Institute for Maternal and Child Health e IRCCS 'Burlo Garofolo', Trieste, Italy., Napolitano LMR; Cluster in Biomedicine, CBM, Trieste, Italy., Maddalo D; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany., Meroni G; Department of Life Sciences, University of Trieste, Italy; Institute for Maternal and Child Health e IRCCS 'Burlo Garofolo', Trieste, Italy. Electronic address: gmeroni@units.it.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2017 Oct; Vol. 1864 (10), pp. 1844-1854. Date of Electronic Publication: 2017 Jul 29.
DOI: 10.1016/j.bbamcr.2017.07.014
Abstrakt: MID1/TRIM18 is a member of the TRIM family of ubiquitin E3 ligases characterized by the presence of a conserved RING-containing N-terminal tripartite motif. Mutations in the MID1 gene have been associated with the X-linked form of Opitz Syndrome, a developmental disorder characterized by midline defects and intellectual disability. The effect of MID1 E3 ligase activity within the cell and the role in the pathogenesis of the disease is still not completely unraveled. Here, we report BRAF35, a non-canonical HMG nuclear factor, as a novel MID1 substrate. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We observed a partial co-localization of the two proteins within cytoplasmic bodies. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance. Our data reveal a novel role for MID1 and for atypical ubiquitination in balancing BRAF35 presence, and likely its activity, within nuclear and cytoplasmic compartments.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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