Distinct developmental expression of Drosophila retinoblastoma factors

Keller, Scott A.; Ullah, Zakir; Buckley, Martin S.; Henry, R. William; Arnosti, David N.

doi:10.1016/j.modgep.2004.09.005

Cited by 21 publications

(31 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For supporting information, Figure S3, embryos were collected from Drosophila melanogaster harboring Flag epitope tagged rbf1 (Acharya et al 2010). Fixing and chromatin preparation was carried out as described in File S1; immunoprecipitations were carried out overnight at 4° using polyclonal rabbit anti-Rbf1 serum (Keller et al 2005). The Rbf1 antibody does not crossreact with Rbf2 on western blots, and it detects only the appropriately sized polypeptide in a western blot of whole embryo extracts (Keller et al 2005).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Evidence for Autoregulation and Cell Signaling Pathway Regulation From Genome-Wide Binding of theDrosophilaRetinoblastoma Protein

Acharya

Nègre

Johnston

et al. 2012

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

The retinoblastoma (RB) tumor suppressor protein is a transcriptional cofactor with essential roles in cell cycle and development. Physical and functional targets of RB and its paralogs p107/p130 have been studied largely in cultured cells, but the full biological context of this family of proteins’ activities will likely be revealed only in whole organismal studies. To identify direct targets of the major Drosophila RB counterpart in a developmental context, we carried out ChIP-Seq analysis of Rbf1 in the embryo. The association of the protein with promoters is developmentally controlled; early promoter access is globally inhibited, whereas later in development Rbf1 is found to associate with promoter-proximal regions of approximately 2000 genes. In addition to conserved cell-cycle–related genes, a wholly unexpected finding was that Rbf1 targets many components of the insulin, Hippo, JAK/STAT, Notch, and other conserved signaling pathways. Rbf1 may thus directly affect output of these essential growth-control and differentiation pathways by regulation of expression of receptors, kinases and downstream effectors. Rbf1 was also found to target multiple levels of its own regulatory hierarchy. Bioinformatic analysis indicates that different classes of genes exhibit distinct constellations of motifs associated with the Rbf1-bound regions, suggesting that the context of Rbf1 recruitment may vary within the Rbf1 regulon. Many of these targeted genes are bound by Rbf1 homologs in human cells, indicating that a conserved role of RB proteins may be to adjust the set point of interlinked signaling networks essential for growth and development.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Although expressed, the Drosophila Rbf1 protein is not functionally required for early cell-cycle regulation in the embryo (Du and Dyson 1999; Stevaux et al 2002; Keller et al 2005). In the mouse, early embryonic requirements for RB are restricted to the trophectoderm, although the protein is expressed in other tissues (Wu et al 2003).…”

mentioning

confidence: 99%

Evidence for Autoregulation and Cell Signaling Pathway Regulation From Genome-Wide Binding of theDrosophilaRetinoblastoma Protein

Acharya

Nègre

Johnston

et al. 2012

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…Stability-Drosophila Rbf proteins are subjected to developmentally regulated turnover, exhibiting tissue-specific modulation in both the developing embryo and the larvae (20,28). To understand the mechanism underlying this regulation, we tested whether the Rbf1-IE can autonomously control protein stability by fusing the IE region (728 -786) to GFP (Fig.…”

Section: A Modular Degron Influences Rbf1 Ubiquitination Andmentioning

confidence: 99%

Ubiquitination of Retinoblastoma Family Protein 1 Potentiates Gene-specific Repression Function

Raj

Zhang

Wei

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Drosophila Rbf1-mediated transcriptional repression of E2F1-dependent genes is canonically regulated by cyclin/cdk-mediated phosphorylation. Results: Rbf1 ubiquitination and turnover is mediated by an evolutionarily conserved C-terminal degron that paradoxically enhances repression of E2F1-dependent genes. Conclusion: Ubiquitination enhances Rbf1 repression potency in a promoter-specific manner. Significance: Rbf1 ubiquitination presents a mechanism for regulatory discrimination of distinct physiological pathways.

show abstract

“…The transcripts of E2f1-regulated replication factor genes are present during the first 16 embryonic cycles even though Rbf1 mRNA and protein are present continuously throughout all of early embryogenesis (Keller et al, 2005;Stevaux et al, 2002). This suggests that embryonic Rbf1 activity is regulated posttranslationally.…”

Section: Phosphorylation Controls the Activity Of Rbf1 In The Early Ementioning

confidence: 99%

Rbf1-independent termination of E2f1-target gene expression during earlyDrosophilaembryogenesis

2007

View full text Add to dashboard Cite

The initiation and maintenance of G1 cell cycle arrest is a key feature of animal development. In the Drosophila ectoderm, G1 arrest first appears during the seventeenth embryonic cell cycle. The initiation of G1 17 arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor. The maintenance of G1 17 arrest requires Rbf1-dependent repression of E2f1-regulated replication factor genes, which are expressed continuously during cycles 1-16 when S phase immediately follows mitosis. The mechanisms that trigger Rbf1 repressor function and mediate G1 17 maintenance are unknown. Here we show that the initial downregulation of expression of the E2f1-target gene RnrS, which occurs during cycles 15 and 16 prior to entry into G1 17 , does not require Rbf1 or p27Dap . This suggests a mechanism for Rbf1-independent control of E2f1 during early development. We show that E2f1 protein is destroyed in a cell cycle-dependent manner during S phase of cycles 15 and 16. E2f1 is destroyed during early S phase, and requires ongoing DNA replication. E2f1 protein reaccumulates in epidermal cells arrested in G1 17 , and in these cells the induction of p27Dap activates Rbf1 to repress E2f1-target genes to maintain a stable G1 arrest.

show abstract

Distinct developmental expression of Drosophila retinoblastoma factors

Cited by 21 publications

References 40 publications

Evidence for Autoregulation and Cell Signaling Pathway Regulation From Genome-Wide Binding of theDrosophilaRetinoblastoma Protein

Evidence for Autoregulation and Cell Signaling Pathway Regulation From Genome-Wide Binding of theDrosophilaRetinoblastoma Protein

Ubiquitination of Retinoblastoma Family Protein 1 Potentiates Gene-specific Repression Function

Rbf1-independent termination of E2f1-target gene expression during earlyDrosophilaembryogenesis

Contact Info

Product

Resources

About