title: Ebi alleviates excessive growth signaling through multiple epigenetic functions in Drosophila.
abstract: As multicellular organisms develop, many cells permanently stop dividing and undergo terminal differentiation. The G1 phase of the cell cycle is thought to be the critical decision point for differentiation. Many growth factors, such as epidermal growth factor, are involved in regulating the G1 to S phase transition, and aberrant activation of growth factor signaling is one of the critical causes of tumor formation. Therefore, each cell must have proper mechanisms to suppress inappropriate/excessive activation of growth factor signaling, but the underlying molecular mechanisms remain undefined. Here, we found that ebi, a Drosophila homologue of genes encoding transducin-β-like 1 and transducin-β-like 1-related protein, mitigated excess growth stimulation by taking advantage of its distinct epigenetic functions. Ebi acted as a corepressor of transcription by forming a complex with retinoblastoma family protein (RBF), a Drosophila homologue of retinoblastoma, and regulating the expression of specific target genes of the Rbf/E2F pathway. Furthermore, ebi also sustained expression of certain genes, including Rbf, encoding factors that inhibit progression out of G1. Our genetic studies suggest that the antagonistic function of ebi against the Polycomb group silencing complex plays a role in the G1/S phase transition.
authors.affiliation: Animal Models of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lim
authors.forename: Yasutoyo
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Leo
authors.initials: L
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D054910:Compound Eye, Arthropod / Q000254:growth & development / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000235:genetics; D005136:Eye Proteins / Q000378:metabolism; D016193:G1 Phase; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D063146:Polycomb-Group Proteins / Q000037:antagonists & inhibitors; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D063146:Polycomb-Group Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C119014:ebi protein, Drosophila; C088084:rux protein, Drosophila; D066246:ErbB Receptors; D019204:GTP-Binding Proteins