p53 is involved in the p120E4F-mediated growth arrest

Sandy, Péter; Gostissa, Monica; Fogal, Valentina; Cecco, Loris De; Szalay, Katalin Sz.; Rooney, Robert J.; Schneider, Claudio; Sal, Giannino Del

doi:10.1038/sj.onc.1203250

Cited by 44 publications

(71 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As previously described in mouse fibroblasts (Sandy et al, 2000;Rizos et al, 2003), the antiproliferative effect of E4F1 in U2OS also appears to depend on the presence of Wt p53 gene and of the direct interaction between the E4F1 and p53 proteins. Accordingly, the growth arrest induced by E4F1 overexpression in U2OS cells is sensitive to short hairpin RNA (shRNA)-mediated depletion of endogenous p53 (Figure 4a) (Brummelkamp et al, 2002).…”

Section: Fhl2 Inhibits E4f1 Repressive Activity On Transcriptionsupporting

confidence: 73%

“…Interestingly, the E4F1-induced G1 arrest appears to depend, at least in part, on pRB and p53 pathways (Fajas et al, 2000;Sandy et al, 2000;Rizos et al, 2003). Consistent with this, E4F1 was found to interact directly in vivo with pRB (Fajas et al, 2000), p53 (Sandy et al, 2000) and p19 ARF (Rizos et al, 2003) and to induce the stabilization of the p21 WAF1 protein (Fernandes et al, 1998). This suggests that E4F1 is somehow involved in both the pRB and p53 pathways.…”

Section: Introductionsupporting

confidence: 52%

“…We and others had previously demonstrated that E4F1 overexpression leads to a strong reduction of DNA synthesis, which results from a cell cycle arrest in G1 (Fernandes et al, 1998;Fajas et al, 2000Fajas et al, , 2001Sandy et al, 2000). To evaluate the impact of FHL2 on E4F-mediated growth arrest, we monitored DNA synthesis in asynchronously growing U2OS cells transiently cotransfected with various combinations of E4F1 and Flag-tagged FHL2, together with GFP expressing plasmids.…”

Section: Fhl2 Antagonizes the P53-dependent Antiproliferative Effectsmentioning

confidence: 99%

“…Indeed, embryos lacking E4F1 die at the peri-implantation stage, while in vitro cultured E4F À/À blastocysts exhibit severe defects in mitotic progression, chromosomal missegregation and increased apoptosis (Le Cam et al, 2004). Conversely, enforced expression of p120 E4F1 in various cell lines inhibits progression from G1 to S phase (Fernandes et al, 1998;Fajas et al, 2000Fajas et al, , 2001Sandy et al, 2000;Rizos et al, 2003;Fenton et al, 2004) and that of p50 E4F1 enhances cell death in E1A/ras-transformed cells (Fernandes et al, 1999). Interestingly, the E4F1-induced G1 arrest appears to depend, at least in part, on pRB and p53 pathways (Fajas et al, 2000;Sandy et al, 2000;Rizos et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, enforced expression of p120 E4F1 in various cell lines inhibits progression from G1 to S phase (Fernandes et al, 1998;Fajas et al, 2000Fajas et al, , 2001Sandy et al, 2000;Rizos et al, 2003;Fenton et al, 2004) and that of p50 E4F1 enhances cell death in E1A/ras-transformed cells (Fernandes et al, 1999). Interestingly, the E4F1-induced G1 arrest appears to depend, at least in part, on pRB and p53 pathways (Fajas et al, 2000;Sandy et al, 2000;Rizos et al, 2003). Consistent with this, E4F1 was found to interact directly in vivo with pRB (Fajas et al, 2000), p53 (Sandy et al, 2000) and p19 ARF (Rizos et al, 2003) and to induce the stabilization of the p21 WAF1 protein (Fernandes et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The LIM-only protein FHL2 is a negative regulator of E4F1

et al. 2006

View full text Add to dashboard Cite

The E1A-targeted transcription factor E4F1 is a key player in the control of mammalian embryonic and somatic cell proliferation and survival. Mouse embryos lacking E4F die at an early developmental stage, whereas enforced expression of E4F1 in various cell lines inhibits cell cycle progression. E4F1-antiproliferative effects have been shown to depend on its capacity to repress transcription and to interact with pRb and p53. Here we show that full-length E4F1 protein (p120 E4F1 ) but not its E1A-activated and truncated form (p50 E4F1 ), interacts directly in vitro and in vivo with the LIM-only protein FHL2, the product of the p53-responsive gene FHL2/ DRAL (downregulated in rhabdomyosarcoma Lim protein). This E4F1-FHL2 association occurs in the nuclear compartment and inhibits the capacity of E4F1 to block cell proliferation. Consistent with this effect, ectopic expression of FHL2 inhibits E4F1 repressive effects on transcription and correlates with a reduction of nuclear E4F1-p53 complexes. Overall, these results suggest that FHL2/DRAL is an inhibitor of E4F1 activity. Finally, we show that endogenous E4F1-FHL2 complexes form in U2OS cells upon UV-light-induced nuclear accumulation of FHL2.

show abstract

Section: Fhl2 Inhibits E4f1 Repressive Activity On Transcriptionsupporting

confidence: 73%

Section: Introductionsupporting

confidence: 52%

Section: Fhl2 Antagonizes the P53-dependent Antiproliferative Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The LIM-only protein FHL2 is a negative regulator of E4F1

et al. 2006

View full text Add to dashboard Cite

show abstract

E4F1 silencing inhibits the cell growth through cell‐cycle arrest in malignant transformed cells induced by hydroquinone

Tan¹,

Jianming

et al. 2018

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Hydroquinone (HQ), one of the most significant metabolic activation products of benzene in an organism, can cause hematological toxicity, such as acute myeloid leukemia. It is a clear carcinogen that can cause changes in the disorder of cell cycle and cell growth. However, its molecular mechanisms remain unclear. E4 transcription factor 1 (E4F1), an important transcription factor, participating in the regulation of cell cycle may be related to the occurrence of tumor. Here, we examined the HQ‐induced malignant transformed TK6 cells (TK6‐HT) to illustrate the role of E4F1 in carcinogenesis. The present study showed that both the expressions of E4F1 messenger RNA and protein increased obviously in TK6‐HT, preliminarily indicating that E4F1 is associated with HQ‐induced carcinogenesis. To further explore the role of E4F1, we established E4F1 silencing TK6‐HT (pLVX‐shE4F1) and its control cells (pLVX‐shNC) using lentiviral short hairpin RNA (shRNA) interference expression plasmid vector pLVX‐shRNA. Flow cytometry and cell counting kit‐8 assay were used to determine the effects of E4F1 silencing on cell cycle and cell growth, respectively. E4F1 silencing inhibited cell growth in TK6‐HT. The results from flow cytometry indicated that the inhibitory effect on cell growth may be the results of the E4F1 silencing–induced accumulation in G2/M compared with TK6‐HT‐shNC. Meanwhile, levels of DNA damage (γ‐H2AX), proteins of Rb and phosphorylated Rb, and reactive oxygen species were increased in TK6‐HT‐shRNA2 cells, which is the critical reason of cell‐cycle arrest. In conclusion, E4F1 silencing inhibits the cell growth through cell‐cycle arrest in malignant transformed cells induced by HQ.

show abstract

Interferon‐stimulated gene 15 enters posttranslational modifications of p53

Wang

Ding

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

The tumor suppressor protein p53 is a central governor of various cellular signals. It is well accepted that ubiquitination as well as ubiquitin-like (UBL) modifications of p53 protein is critical in the control of its activity. Interferon-stimulated gene 15 (ISG15) is a well-known UBL protein with pleiotropic functions, serving both as a free intracellular molecule and as a modifier by conjugating to target proteins. Initially, attentions have historically focused on the antiviral effects of ISG15 pathway. Remarkably, a significant role in the processes of autophagy, DNA repair, and protein translation provided considerable insight into the new functions of ISG15 pathway. Despite the deterministic revelation of the relation between ISG15 and p53, the functional consequence of p53 ISGylation appears somewhat confused. More important, more recent studies have hinted p53 ubiquitination or other UBL modifications that might interconnect with its ISGylation. Here, we aim to summarize the current knowledge of p53 ISGylation and the differences in other significant modifications, which would be beneficial for the development of p53-based cancer therapy. K E Y W O R D S estrogen-responsive finger protein, HECT and RLD domain containing E3 ubiquitin protein ligase 5, p53 ISGylation, ubiquitin-like proteins

show abstract

p53 is involved in the p120E4F-mediated growth arrest

Cited by 44 publications

References 38 publications

The LIM-only protein FHL2 is a negative regulator of E4F1

The LIM-only protein FHL2 is a negative regulator of E4F1

E4F1 silencing inhibits the cell growth through cell‐cycle arrest in malignant transformed cells induced by hydroquinone

Interferon‐stimulated gene 15 enters posttranslational modifications of p53

Contact Info

Product

Resources

About