Mutation of the DEAD-box helicase belle downregulates the cyclin-dependent kinase inhibitor Dacapo.
The retinoblastoma protein (pRB) negatively regulates cell proliferation by limiting the activity of the family of E2F transcription factors. In Drosophila, mutation of the DEAD-box helicase belle (bel) relieves an E2F/pRB induced G(1) cell cycle arrest; however, the mechanism of this rescue is unknown. Here, we show that the level of the cyclin-dependent kinase inhibitor Dacapo (Dap), homolog of mammalian p21/p27, is strongly reduced both in bel mutant cells in vivo and in tissue culture cells depleted of Bel by RNA interference. Interestingly, the loss of bel also partially alleviates an ectopically induced G(1) cell cycle arrest. Additionally, we show that Bel undergoes nucleocytoplasmic shuttling. Thus, inactivation of bel renders cells less sensitive to several anti-proliferative signals inducing G(1) arrest.
Ambrus
Aaron M
AM
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
Frolov
Maxim V
MV
D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000378:metabolism; D016193:G1 Phase; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors
D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D009687:Nuclear Proteins; D014157:Transcription Factors; C103336:dap protein, Drosophila; C490120:Ddx1 protein, Drosophila; D053487:DEAD-box RNA Helicases