title: Inter-isoform-dependent Regulation of the Drosophila Master Transcriptional Regulator SIN3.
abstract: SIN3 is a transcriptional corepressor that acts as a scaffold for a histone deacetylase (HDAC) complex. The SIN3 complex regulates various biological processes, including organ development, cell proliferation, and energy metabolism. Little is known, however, about the regulation of SIN3 itself. There are two major isoforms of Drosophila SIN3, 187 and 220, which are differentially expressed. Intrigued by the developmentally timed exchange of SIN3 isoforms, we examined whether SIN3 187 controls the fate of the 220 counterpart. Here, we show that in developing tissue, there is interplay between SIN3 isoforms: when SIN3 187 protein levels increase, SIN3 220 protein decreases concomitantly. SIN3 187 has a dual effect on SIN3 220. Expression of 187 leads to reduced 220 transcript, while also increasing the turnover of SIN3 220 protein by the proteasome. These data support the presence of a novel, inter-isoform-dependent mechanism that regulates the amount of SIN3 protein, and potentially the level of specific SIN3 complexes, during distinct developmental stages.
authors.affiliation: From the Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and.
authors.forename: Ashlesha
authors.initials: A
authors.lastname: Chaubal
authors.affiliation: the Department of Pharmacology, Wayne State University, Detroit, Michigan 48201.
authors.forename: Sokol V
authors.initials: SV
authors.lastname: Todi
authors.affiliation: From the Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and loripile@wayne.edu.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Pile
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D020033:Protein Isoforms; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056264:Sin3 Histone Deacetylase and Corepressor Complex
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D046988:Proteasome Endopeptidase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex
keywords: Drosophila; SIN3; gene transcription; histone modification; proteasome; protein stability