DNA damage-inducible gene
            <i>p33ING2</i>
            negatively regulates cell proliferation through acetylation of p53

Nagashima, Makoto; Sekiguchi, Masayuki; Miura, Koh; Hagiwara, Koichi; Linke, Steven P.; Pedeux, Rémy; Wang, Xin Wei; Yokota, Jun; Riabowol, Karl; Harris, Curtis C.

doi:10.1073/pnas.161151798

Cited by 177 publications

(247 citation statements)

References 52 publications

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“…ING1 downregulation was observed in different tumor types (breast, gastric, esophageal, blood, lung and brain) (Gong et al, 2005), whereas protein mislocalization was described in tumors of different origin (Nouman et al, 2002). ING2 expression was reduced in colorectal, hepatocellular carcinoma, prostate, pancreatic, lung cancer and cutaneous melanoma (Nagashima et al, 2001;Lu et al, 2006;Okano et al, 2006). Allelic loss and reduced expression of ING3 have been also reported (Gunduz et al, 2002;Nagashima et al, 2003).…”

Section: Introductionmentioning

confidence: 86%

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Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

et al. 2007

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Inhibitor of growth (ING)4, member of a gene family encoding potential tumor suppressors, is implicated as a repressor of angiogenesis and tumor growth and suppresses loss of contact inhibition in vitro. Here, we report that ING4 undergoes alternative splicing. Expression analysis identified novel ING4 spliced variant mRNAs encoding proteins devoid of different portions. The ING4 variants were detected in both normal and tumor tissues. The existence of ING4 variants was confirmed by several approaches, including reverse transcriptase-polymerase chain reaction, real-time PCR and in silico experiments. To investigate the functional consequences of alternative splicing the ING4 variant cDNAs were expressed in mammalian cells. Our studies indicated that (i) the ING4 variants do not differ from wild-type in their nuclear localization, interaction with p53 and association to HBO1 complex; and (ii) the ING4-DEx6A variant, devoid of the C-terminal portion, loses the capability to inhibit NF-jB. On the whole our data suggest that alternative splicing could modulate the activity of ING4 tumor suppressor protein.

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Section: Introductionmentioning

confidence: 86%

“…A physical association between ING proteins and p53 has been reported in different studies. Furthermore, ING proteins may modulate p53 activity by enhancing p53 acetylation at Lys-382 (Nagashima et al, 2001;Kataoka et al, 2003;Russell et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

et al. 2007

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“…The founding member of the family, ING1, was initially discovered by a screen designed to identify genes that allow neoplastic transformation when repressed (Garkavtsev et al, 1996). Subsequently, four other members of the family, ING2-ING5, were identified by a homology search (Nagashima et al, 2001Shiseki et al, 2003). INGs are nuclear proteins and one important structural feature of these proteins is the presence of a highly conserved plant homeodomain zinc-finger in their C-terminal part.…”

Section: Introductionmentioning

confidence: 99%

“…The interaction between ING2 and this modified histone allows the stabilization of the Sin3A/HDAC complex onto the promoter of the proliferative genes c-myc and cyclin D1 to mediate their repression (Shi et al, 2006). Initially, ING2 was reported to enhance p53 acetylation to negatively regulate cell growth, to induce apoptosis and to regulate the onset of replicative senescence (Nagashima et al, 2001;Pedeux et al, 2005). In these pathways, it has been reported that the lipid signaling molecule phosphatidylinositol-5-phosphate binds and activates ING2 (Gozani et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Sumoylation of ING2 regulates the transcription mediated by Sin3A

et al. 2010

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ING2 (inhibitor of growth 2) is a candidate tumorsuppressor gene involved in cell cycle control, apoptosis and senescence. Although the functions of ING2 within the chromatin remodeling complex Sin3A/histone deacetylase (HDAC) and in the p53 pathway have been described, how ING2 itself is regulated remains unknown. In this study we report for the first time that ING2 can be sumoylated by small ubiquitin-like modifier 1 (SUMO1) on lysine 195 both in vitro and in vivo. Strikingly, ING2 sumoylation enhances its association with Sin3a. We provide evidences that ING2 can bind to the promoter of genes to mediate their expression and that sumoylation of ING2 is required for this binding to some of these genes. Among them, we identified the gene TMEM71 (transmembrane protein 71), whose expression is regulated by ING2 sumoylation. ING2 must be sumoylated to bind to the promoter of TMEM71 and to recruit the Sin3A chromatin-modifying complex to this promoter, in order to regulate TMEM71 transcription. Hence, sumoylation of ING2 enhances its binding to the Sin3A/HDAC complex and is required to regulate gene transcriptions.

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“…ING5) are implicated in a variety of processes including gene transcription, oncogenesis, apoptosis, DNA repair, and cell cycle control (Nagashima et al, 2001Feng et al, 2002;Shiseki et al, 2003;Campos et al, 2004). ING4, a novel member of the ING family, has recently emerged as a strong tumor suppressor gene that functions in cell proliferation, contact inhibition, and angiogenesis (Garkavtsev et al, 2004;Kim et al, 2004).…”

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confidence: 99%

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

Li¹,

Cai²,

Liang³

et al. 2008

The Anatomical Record

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ING4, as a novel candidate tumor suppressor gene, has been implicated in several human malignances by tumor growth inhibition and apoptosis enhancement. The mechanism of ING4 remains largely unknown. The purpose of this study was to investigate the inhibitory tumor growth effects of ING4 on lung adenocarcinoma, and its mechanism, by ING4 cDNA transduction into A549 cells. Furthermore, the expression level of ING4 in lung adenocarcinoma tissues was examined. The expression of ING4 was markedly reduced in human lung adenocarcinoma tissues. Overexpression of ING4 can induce growth inhibition in A549 cells both in vitro and in vivo, and also induce up-regulation of p27, down-regulation of cyclinD1, SKP2, and Cox2, and inactivation of the Wnt-1/b-catenin pathway. Moreover, overexpression of ING4 can enhance the sensitivity of A549 cells to radiotherapy and chemotherapy. Thus, ING4 may play an inhibitory role on A549 cell proliferation and tumor growth in lung adenocarcinoma by up-regulation or down-regulation of cell proliferation-regulating proteins such as p27, cyclinD1, SKP2, and Cox2 by means of inactivation of Wnt-1/b-catenin signaling.

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DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53

Cited by 177 publications

References 52 publications

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

Sumoylation of ING2 regulates the transcription mediated by Sin3A

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

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