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1.  Loss of dE2F compromises mitochondrial function 
Developmental cell  2013;27(4):10.1016/j.devcel.2013.10.002.
SUMMARY
E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we investigated the mechanism of the resistance of Drosophilad DP mutants to irradiation-induced apoptosis. Contrary to the prevailing view, this is not due to an inability to induce the apoptotic transcriptional program, since we show that this program is induced, but rather due to a mitochondrial dysfunction of dDP mutants. We attribute this defect to E2F/DP-dependent control of expression of mitochondria associated genes. Genetic attenuation of several of these E2F/DP targets mimics the dDP mutant mitochondrial phenotype and protects from irradiation-induced apoptosis. Significantly, the role of E2F/DP in the regulation of mitochondrial function is conserved between flies and humans. Thus, our results uncovered a role of E2F/DP in the regulation of mitochondrial function and demonstrate that this aspect of E2F regulation is critical for the normal induction of apoptosis in response to irradiation.
doi:10.1016/j.devcel.2013.10.002
PMCID: PMC3866969  PMID: 24286825
dE2f1 transcription factor; Drosophila; apoptosis
2.  Mutation of the DEAD-box helicase belle down-regulates the cyclin-dependent kinase inhibitor Dacapo 
Cell cycle (Georgetown, Tex.)  2010;9(5):1016-1020.
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 G1 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 G1 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 G1 arrest.
PMCID: PMC3015103  PMID: 20160476
Retinoblastoma protein; E2F transcription factor; cyclin dependent kinase inhibitor; Drosophila; DEAD-box protein
3.  The Diverse Roles of RNA Helicases in RNAi 
Cell cycle (Georgetown, Tex.)  2009;8(21):3500-3505.
RNA interference (RNAi) is a regulatory gene silencing system found in nearly all eukaryotic organisms that employs small RNAs, typically 20–25 nucleotides long, to target complementary sequences found in mRNAs. RNA helicases use ATP to unwind double-stranded RNA (dsRNA), and are known to participate at nearly every level of RNA metabolism. A multitude of RNA helicases have been isolated from screens for essential RNAi factors, and even the earliest models of the RNAi pathway have presumed an RNA helicase to function at the level of small RNA duplex unwinding. However, while many components that function in RNAi have been uncovered and characterized, the exact placement in the pathway and ascription of a specific biochemical function of an RNA helicase in RNAi remains elusive. Recent studies have delved deeper into the precise role of some RNA helicases. Surprisingly, these studies have revealed nontraditional roles, which may not even require the helicase activity. Such findings suggest that RNA helicases regulate gene silencing at nearly every level of the RNAi pathways.
PMCID: PMC3016640  PMID: 19823018
gene silencing; RNA helicase; RNAi; small RNAs; unwind
4.  dE2F2-Independent Rescue of Proliferation in Cells Lacking an Activator dE2F1▿  
Molecular and Cellular Biology  2007;27(24):8561-8570.
In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.
doi:10.1128/MCB.01068-07
PMCID: PMC2169406  PMID: 17923695

Results 1-4 (4)