Specific role of the SR protein splicing factor B52 in cell cycle control in Drosophila.
E2F and retinoblastoma tumor suppressor protein pRB are important regulators of cell proliferation; however, the regulation of these proteins in vivo is not well understood. In Drosophila there are two E2F genes, an activator, de2f1, and a repressor, de2f2. The loss of de2f1 gives rise to the G(1)/S block accompanied by the repression of E2F-dependent transcription. These defects can be suppressed by mutation of de2f2. In this work, we show that the de2f1 mutant phenotype is rescued by the loss of the pre-mRNA splicing factor SR protein B52. Mutations in B52 restore S phase in clones of de2f1 mutant cells and phenocopy the loss of the de2f2 function. B52 acts upstream of de2f2 and plays a specific role in regulation of de2f2 pre-mRNA splicing. In B52-deficient cells, the level of dE2F2 protein is severely reduced and the expression of dE2F2-dependent genes is deregulated. Reexpression of the intronless copy of dE2F2 in B52-deficient cells restores the dE2F2-mediated repression. These results uncover a previously unrecognized role of the splicing factor in maintaining the G(1)/S block in vivo by specific regulation of the dE2F2 repressor function.
Rasheva
Vanya I
VI
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, MBRB 2352, MC 669, 900 S. Ashland Ave., Chicago, IL 60607, USA.
Knight
David
D
Bozko
Przemyslaw
P
Marsh
Katherine
K
Frolov
Maxim V
MV
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D050703:E2F2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000033:anatomy & histology / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000378:metabolism; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C496298:E2f1 protein, Drosophila; C115434:E2f2 protein, Drosophila; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C070791:B52 protein, Drosophila