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Biochim Biophys Acta Gene Regul Mech 2023 Mar 01;18661:194901. doi: 10.1016/j.bbagrm.2022.194901.
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OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development.

Job F , Mai C , Villavicencio-Lorini P , Herfurth J , Neuhaus H , Hoffmann K , Pfirrmann T , Hollemann T .

Ubiquitination and deubiquitylation regulate essential cellular processes and involve hundreds of sequentially acting enzymes, many of which are barely understood. OTUD3 is an evolutionarily highly conserved deubiquitinase involved in many aspects of cellular homeostasis. However, its biochemical properties and physiological role during development are poorly understood. Here, we report on the expression of OTUD3 in human tissue samples where it appears prominently in those of neuronal origin. In cells, OTUD3 is present in the cytoplasm where it can bind to microtubules. Interestingly, we found that OTUD3 cleaves preferentially at K6 and K63, i.e., poly-ubiquitin linkages that are not primarily involved in protein degradation. We employed Xenopus embryos to study the consequences of suppressing otud3 function during early neural development. We found that Otud3 deficiency led to impaired formation of cranial and particularly of cranial neural crest-derived structures as well as movement defects. Thus, OTUD3 appears as a neuronally enriched deubiquitinase that is involved in the proper development of the neural system.

PubMed ID: 36503125
Article link: Biochim Biophys Acta Gene Regul Mech

Species referenced: Xenopus laevis
Genes referenced: bmp4 foxd3 gba1 ncam1 odc1 otud1 otud3 otud4 otud5 otud6b otud7a otud7b pax6 sox10 tbxt tubb2b twist1 yod1
Antibodies: Smad1 Ab8
Morpholinos: otud3 MO1 otud3 MO2

Phenotypes: Xla Wt + otud3 MO (Fig. 4. FGH) [+]

Article Images: [+] show captions