Disease relevance of ING2

• Nuclear ING2 expression is reduced in human cutaneous melanomas [1].
• Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P < 0.05) [1].
• Loss of heterozygosity on chromosome 4q32-35 in sporadic basal cell carcinomas: evidence for the involvement of p33ING2/ING1L and SAP30 genes [2].
• In addition, we found that p33ING2 is an essential factor for UV-induced rapid histone H4 acetylation, chromatin relaxation, and the recruitment of damage recognition protein, xeroderma pigmentosum group A protein, to the photolesions [3].
• Although the significance of this observation with respect to carcinogenesis remains to be established, the data suggest that ING1L might be involved in colon cancers through interference with signal(s) transmitted through p53 and p33(ING1) [4].

High impact information on ING2

• Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can regulate p53 and histone acetylation in response to cellular stress and contains a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5-phosphate (PtdIns5P) [5].
• Three exons overlap with ING2 (a putative tumor suppressor) and with a homologue of CIS4 (cytokine-inducible SH2 protein 4), both of which are encoded by the opposite strand [6].
• DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53 [7].
• ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation [8].
• ING2 is a candidate tumor suppressor gene that can activate p53 by enhancing its acetylation [8].

Biological context of ING2

• Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382 [7].
• The level of ING2 expression directly modulated the onset of replicative senescence [8].
• While overexpression of ING2 induced senescence in young fibroblasts in a p53-dependent manner, expression of ING2 small interfering RNA delayed the onset of senescence [8].
• In contrast to ING2, ING4 is not a phosphoinositide receptor and binds with similar affinity to the different methylation states of histone-3 at lysine 4 [9].
• Further analyses indicate that the minimal deleted region in 4q32-35 includes p33ING2/ING1L and SAP30, whose deletion could impair the G1-phase checkpoint control and favor gene silencing, respectively [2].

Anatomical context of ING2

• Moreover, we found that p33ING2 promoted Bax translocation to mitochondria, altered the mitochondrial membrane potential, and induced cytochrome c release and thus the activation of caspases 9 and 3 [10].

Associations of ING2 with chemical compounds

• ING2 protein expression increased in late-passage human primary cells, and it colocalizes with serine 15-phosphorylated p53 [8].
• The family of proteins inhibitors of growth (ING) contains a PHD finger that bind to histone-3 trimethylated at lysine 4, and those of ING1 and ING2 also act as nuclear phosphoinositide receptors [9].

Regulatory relationships of ING2

• Knockdown of endogenous SnoN blocks the ability of ING2 to promote TGF-beta-dependent transcription, and conversely expression of SnoN augments ING2 enhancement of the TGF-beta response [11].

Other interactions of ING2

• Three submotifs MDS00105.1-3 are specific for ING1/ING1L, ING1-homolog, and ING3 subfamilies [12].
• Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor [4].
• Leucine zipper-like domain is required for tumor suppressor ING2-mediated nucleotide excision repair and apoptosis [13].

Analytical, diagnostic and therapeutic context of ING2

• Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies [1].
• Fluorescence in situ hybridization and radiation-hybrid analyses assigned ING1L to human chromosome 4 [4].

References