title: Drosophila models reveal novel insights into mechanisms underlying neurodegeneration.
abstract: The SAGA chromatin modifying complex functions as a transcriptional coactivator for a large number of genes, and SAGA dysfunction has been linked to carcinogenesis and neurodegenerative disease. The protein complex is comprised of approximately 20 subunits, arranged in a modular fashion, and includes 2 enzymatic subunits: the Gcn5 acetyltransferase and the Non-stop deubiquitinase. As we learn more about SAGA, it becomes evident that this complex functions through sophisticated mechanisms that support very precise regulation of gene expression. Here we describe recent findings in which a Drosophila loss-of-function model revealed novel mechanisms for regulation of SAGA-mediated histone H2B deubiquitination. This model also yielded novel and surprising insights into mechanisms that underlie progressive neurodegenerative disease. Lastly, we comment on the utility of Drosophila as a model for neurodegenerative disease through which crucial and conserved mechanisms may be revealed.
authors.affiliation: a Stowers Institute for Medical Research ; Kansas City , MO USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Mohan
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
mesh_terms: D000818:Animals; D000067719:Ataxin-7; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D000067719:Ataxin-7; D029721:Drosophila Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; C527172:Sgf11 protein, Drosophila; D014157:Transcription Factors; C423782:e(y)2 protein, Drosophila; D010450:Endopeptidases; C421164:not protein, Drosophila
keywords: Ataxin-7; CAG repeat; Drosophila; H2B ubiquitination; H2Bub; Non-stop; PolyQ; SAGA complex; SCA7; USP22; chromatin; neurodegenerative disease; polyglutamine expansion; retinal and macular degeneration; spinocerebellar ataxia 7; transcription; transcriptional coactivator