ING1 and ING2: multifaceted tumor suppressor genes

Abstract

Inhibitor of Growth 1 (ING1) was identified and characterized as a "candidate" tumor suppressor gene in 1996. Subsequently, four more genes, also characterized as "candidate" tumor suppressor genes, were identified by homology search: ING2, ING3, ING4, and ING5. The ING proteins are characterized by a high homology in their C-terminal domain, which contains a Nuclear Localization Sequence and a Plant HomeoDomain (PHD), which has a high affinity to Histone 3 tri-methylated on lysine 4 (H3K4Me3). The ING proteins have been involved in the control of cell growth, senescence, apoptosis, chromatin remodeling, and DNA repair. Within the ING family, ING1 and ING2 form a subgroup since they are evolutionarily and functionally close. In yeast, only one gene, Pho23, is related to ING1 and ING2 and possesses also a PHD. Recently, the ING1 and ING2 tumor suppressor status has been fully established since several studies have described the loss of ING1 and ING2 protein expression in human tumors and both ING1 and ING2 knockout mice were reported to have spontaneously developed tumors, B cell lymphomas, and soft tissue sarcomas, respectively. In this review, we will describe for the first time what is known about the ING1 and ING2 genes, proteins, their regulations in both human and mice, and their status in human tumors. Furthermore, we explore the current knowledge about identified functions involving ING1 and ING2 in tumor suppression pathways especially in the control of cell cycle and in genome stability.

Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration

“…ASCL1 (MASH1), a transcription factor with critical roles in neuronal commitment and in fibroblastneuron in vitro transdifferentiation was essential for hESC-derived neural lineage development (18). Enrichment of shRNAs during NPC generation is illustrated by shRNAs silencing ING5, a tumor suppressor protein that inhibits growth of various cell types (19).…”

Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia

“…We identified several genes encoding proteins known to be involved in cell cycle regulation to be dysregulated. CDKN1A (fold change (fc = −4.94), inhibitor of growth family member 4 and 5 (ING4) (fc = 2.94) and (ING5) (fc = 2.13), tumour protein and TP53 inducible protein 3 (TP53I3) (fc = 2.92), centromere protein O (CENPO) (fc = −2.21) and proteasome activator complex subunit 3 (PSME3) (fc = −2.26)19, 20, 21, 22 were significantly altered in CLL compared to healthy donor samples (Figure 3A and Supporting Information). In addition, genes encoding proteins involved in centrosome assembly and function such as centromere protein T (CENPT) (fc = 2.94) and centromere protein J (CENPJ) (fc = 2.08) were up‐regulated in CLL compared to healthy samples (Figure 3A).…”

Inhibitors of Growth 1b Suppresses Peroxisome Proliferator-Activated Receptor-β/δ Expression Through Downregulation of Hypoxia-Inducible Factor 1α in Osteoblast Differentiation

“…A recent study found that inhibitors of growth (ING) 1b may decrease osteoblast marker expression, including Runx2 (Bigot et al, 2015). ING1, a member of the ING family, has been described as a type II tumor suppressor that can regulate cell growth, apoptosis, chromatin remodeling, senescence, cell cycle regulation, and DNA repair (Garkavtsev et al, 1998;Guérillon et al, 2013). The human ING1 gene contains three exons and is located at chromosome 13q33-34 Feng et al, 2002).…”