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- W1969945563 abstract "ABSTRACT Ubiquitin conjugation typically requires three classes of enzyme: E1, E2, and E3. A fourth type of enzyme (E4), however, was recently shown to be required for the degradation of certain types of substrate in yeast. We previously identified UFD2a (also known as E4B) as an E4 in mammals. UFD2a is exclusively expressed in cardiac muscle during mouse embryonic development, but it is abundant in neurons of adult mice and is implicated in the pathogenesis of neurodegenerative disease. The precise physiological function of this enzyme has remained largely unknown, however. Here, we show that mice lacking UFD2a die in utero, manifesting marked apoptosis in the developing heart. Polyubiquitylation activity for an E4 substrate was greatly reduced in Ufd2a −/− mouse embryonic fibroblasts. Furthermore, Ufd2a +/− mice displayed axonal dystrophy in the nucleus gracilis, as well as degeneration of Purkinje cells accompanied by endoplasmic reticulum stress. These animals also developed a neurological disorder. UFD2a thus appears to be essential for the development of cardiac muscle, as well as for the protection of spinocerebellar neurons from degeneration induced by endoplasmic reticulum stress." @default.
- W1969945563 created "2016-06-24" @default.
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- W1969945563 date "2005-12-15" @default.
- W1969945563 modified "2023-10-16" @default.
- W1969945563 title "Mammalian E4 Is Required for Cardiac Development and Maintenance of the Nervous System" @default.
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- W1969945563 doi "https://doi.org/10.1128/mcb.25.24.10953-10964.2005" @default.
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