Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression.

Johnson, D. Gale; Ohtani, Kiyoshi; Nevins, Joseph R.

doi:10.1101/gad.8.13.1514

Cited by 487 publications

(520 citation statements)

References 66 publications

Supporting

Mentioning

477

Contrasting

Unclassified

Order By: Relevance

“…As shown in Figure 6, CAT transcript level is almost undetectable when the cells are quiescent (G0/G1 phase), whereas 12 h following the addition of serum, which corresponds to the G1/S transition, the CAT transcript level peaks. Therefore, the quail E2F-1 transcription is also strongly activated at the G1/S transition, as has been shown for the human and murine homologs of the E2F-1 gene (Johnson et al 1994;Hsiao 1994;Neuman et al, 1996). This result also indicates that the proE2F-CAT construct possesses most, if not all, regulatory elements allowing regulation of E2F-1 transcription in a cell cycle-dependent manner.…”

Section: Regulation Of E2f-1 Promoter Activity During the Cell Cyclesupporting

confidence: 70%

“…Analysis of the sequence of the promoter region also shows a good conservation between mammalian and avian species, especially near the two double E2F binding sites found as tandem repeats close to the transcription start site (Johnson et al, 1994;Hsiao et al, 1994;Neuman et al, 1996). Analysis of E2F-1 gene expression during the cell cycle has shown that this gene is only activated at the G1/S transition, like its mammalian homologs (Johnson et al 1994;Hsiao, 1994;Neuman et al, 1996).…”

Section: Discussionmentioning

confidence: 93%

“…Position of relevant restriction site is indicated. (c) Multiple alignment of promoter regions of E2F-1 genes from quail, mouse (Hsiao et al, 1994) and human (Johnson et al, 1994). Identical nucleotides are shaded.…”

Section: Organization Of Quail E2f-1 Genementioning

confidence: 99%

See 2 more Smart Citations

Regulation of E2F-1 gene expression in avian cells

et al. 1998

View full text Add to dashboard Cite

E2F-1 is the prototype of a family of transcription factors playing a central role in the control of cell proliferation and apoptosis. E2F DNA binding activity is down-regulated during cellular di erentiation, which is correlated with cell division arrest. We report here that the expression of E2F-1 itself is down-regulated in the developing quail neural retina between embryonic days E8-E10. This event occurs just after the massive arrest of the quail neuroretina cell division (E7-E8). To gain further insight into the regulatory mechanisms monitoring E2F-1 expression in di erentiating neurons, we have cloned the quail E2F-1 promoter. In vivo DNA footprintings of this promoter have shown that a number of potential SP-1 and C/EBP response elements are constitutively occupied in the entire quail neuroretina of E5 and E14, whereas the two consensus palindromic E2F binding sites are only protected at E5. This suggests that these E2F elements participate in down-regulation of E2F-1 gene expression during avian neuroretina development. CAT reporter assays have shown that E2F-1 in association with its partner DP-1 transactivates its own promoter, whereas p105 Rb inhibits the E2F-1 promoter. Both E2F-1/DP-1 and p105 Rb require the presence of the E2F binding sites to mediate their e ects. However, experiments performed with deletion mutants of the promoter strongly suggest that other regions located upstream of the E2F binding sites also mediate part of the E2F-1 transactivating e ect on its own promoter. Altogether, these results suggest that the down-regulation of E2F-1 gene expression in di erentiating neurons could be due, in part, to the E2F/Rb complexes binding to the E2F-1 promoter.

show abstract

Section: Regulation Of E2f-1 Promoter Activity During the Cell Cyclesupporting

confidence: 70%

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Regulation of E2F-1 gene expression in avian cells

et al. 1998

View full text Add to dashboard Cite

show abstract

“…As a control we used the GAPDH gene ( Figure 4b) which displays only modest cell cycle variations in rodent ®broblast (Johnson et al, 1994). As anticipated from previous results with other mouse ®broblasts (Slansky and Farnham, 1996), there was signi®cant E2F-3 mRNA present in the quiescent cells.…”

Section: E2f-3 Accumulation Peaks During Dna Synthesis In Both Normalmentioning

confidence: 77%

E2F-3 accumulation is regulated by polypeptide stability

1998

Oncogene

View full text Add to dashboard Cite

E2F is a complex family of transcription factors which appears to regulate the transcription of genes required for the S phase of the mammalian cell cycle. In the present work, we have examined the mechanisms regulating E2F-3 accumulation in mouse ®broblasts. We have determined that E2F-3 DNA binding activity is restricted to the G 1 /S transition and S phase in both normal BALB/c-3T3 ®broblasts and in an SV40 virustransformed BALB/c-3T3 derivative. Immunoblot analysis indicates that G 0 and G 1 cells have little or no E2F-3 polypeptide and that the increase in the DNA binding activity of E2F-3 at the G 1 /S boundary is re¯ected by an increase in total E2F-3 protein. In contrast to the E2F-3 polypeptide, RNAse protection assays demonstrate that the E2F-3 mRNA is clearly present in G 0 and G 1 cells. Finally, pulse/chase experiments indicate that the halflife of E2F-3 is approximately 40-fold greater in cells blocked in S phase relative to asynchronously growing cells. Together, these results indicate that the accumulation E2F-3 at S phase may be regulated, at least in part, at the level of protein stability.

show abstract

“…6g). Given the autoregulatory control of E2F1 expression,28 decreases in E2F1 protein levels are assumed to reduce the activity of the E2F1 promoter, thereby leading to the downregulation of the entire E2F1‐mediated transcriptional network.…”

Section: Discussionmentioning

confidence: 99%

Linkage of E2F1 transcriptional network and cell proliferation with respiratory chain activity in breast cancer cells

et al. 2016

View full text Add to dashboard Cite

Mitochondria are multifunctional organelles; they have been implicated in various aspects of tumorigenesis. In this study, we investigated a novel role of the basal electron transport chain (ETC) activity in cell proliferation by inhibiting mitochondrial replication and transcription (mtR/T) using pharmacological and genetic interventions, which depleted mitochondrial DNA/RNA, thereby inducing ETC deficiency. Interestingly, mtR/T inhibition did not decrease ATP levels despite deficiency in ETC activity in different cell types, including MDA‐MB‐231 breast cancer cells, but it severely impeded cell cycle progression, specifically progression during G2 and/or M phases in the cancer cells. Under these conditions, the expression of a group of cell cycle regulators was downregulated without affecting the growth signaling pathway. Further analysis suggested that the transcriptional network organized by E2F1 was significantly affected because of the downregulation of E2F1 in response to ETC deficiency, which eventually resulted in the suppression of cell proliferation. Thus, in this study, the E2F1‐mediated ETC‐dependent mechanism has emerged as the regulatory mechanism of cell cycle progression. In addition to E2F1, FOXM1 and BMYB were also downregulated, which contributed specifically to the defects in G2 and/or M phase progression. Thus, ETC‐deficient cancer cells lost their growing ability, including their tumorigenic potential in vivo. ETC deficiency abolished the production of reactive oxygen species (ROS) from the mitochondria and a mitochondria‐targeted antioxidant mimicked the deficiency, thereby suggesting that ETC activity signaled through ROS production. In conclusion, this novel coupling between ETC activity and cell cycle progression may be an important mechanism for coordinating cell proliferation and metabolism.

show abstract

Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression.

Cited by 487 publications

References 66 publications

Regulation of E2F-1 gene expression in avian cells

Regulation of E2F-1 gene expression in avian cells

E2F-3 accumulation is regulated by polypeptide stability

Linkage of E2F1 transcriptional network and cell proliferation with respiratory chain activity in breast cancer cells

Contact Info

Product

Resources

About