The ING tumor suppressor genes: Status in human tumors

Guérillon, Claire; Bigot, Nicolas; Pedeux, Rémy

doi:10.1016/j.canlet.2013.11.016

Cited by 49 publications

(53 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have made clear that p21 expression can be regulated through p53 dependent or independent signaling pathway [10, 16]. To examine whether ING4 regulated p21 expression was dependent on p53 expression, the p53 +/+ HCT116 and p53 −/− HCT116 cells were used.…”

Section: Resultsmentioning

confidence: 99%

“…Cell cycle protein, inhibitor of growth protein 4 (ING4), one member of INGs, possess a common schematic structure, including a Plant Homeo Domain, a Nuclear Localisation Signal and a Novel Conserved Region [10]. ING4 has been identified as an important tumor suppressor gene, which is involved in cell cycle arrest, apoptosis, DNA repair, chromatin modification, inhibiting cell migration and angiogenesis [10–12].…”

Section: Introductionmentioning

confidence: 99%

“…ING4 has been identified as an important tumor suppressor gene, which is involved in cell cycle arrest, apoptosis, DNA repair, chromatin modification, inhibiting cell migration and angiogenesis [10–12]. Recent studies have indicated that both mRNA and protein levels of ING4 are lost or decreased in CRC when compared with normal colon tissues [13, 14].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

et al. 2016

View full text Add to dashboard Cite

ING4, a potential tumor suppressor, is implicated in cell cycle arrest, apoptosis, cell migration and angiogenesis. Here, we investigated the clinical value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this study, we found that ING4 expression was significantly reduced in CRC tissues versus paired normal colon tissues. Moreover, low ING4 expression was significantly associated with increased lymph node metastasis, advanced TNM stage and poor overall survival. Multivariate Cox regression analysis showed that ING4 expression was an independent favourable prognostic factor for CRC (hazard ratio = 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC angiogenesis by suppressing Sp1 expression and transcriptional activity through ubiquitin degradation and down-regulating the expressions of Sp1 downstream pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by inducing p21 expression in despite of p53 status. Our findings imply that reduced ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for the treatment of metastatic CRC.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…ING proteins are broadly lost or mutated in various types of human cancers (15, 16). Overexpression studies suggest their involvement in preventing cellular proliferation, while enhancing cell contact inhibition and DNA damage-induced cell death (12).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3

Kim

Natesan

Cornilescu

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 μm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD-H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities.

show abstract

“…For review : Ythier et al, 2008;Guérillon et al, 2014. Many genetics and epigenetics alterations of tumor suppressor genes (TSGs) or oncogenes contribute to cancerogenesis.…”

Section: Various Cancersmentioning

confidence: 99%