ING1 and ING2: Multi-Faceted Tumor Suppressor Genes

Claire Guérillon (1) , Delphine Larrieu (2) , Rémy Pedeux (1)

1 MiCa - Microenvironnement et cancer
2 Chercheur indépendant

ING1 (Inhibitor of Growth 1) 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 (NLS) 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 remodelling 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 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.

Mots clés: ING1; ING2; Tumor suppressor gene; p53; H3K4Me3

Domaines: Cancer; Biologie cellulaire; Biochimie, Biologie Moléculaire

Claire Guérillon, Delphine Larrieu, Rémy Pedeux. ING1 and ING2: Multi-Faceted Tumor Suppressor Genes. Cellular and Molecular Life Sciences, 2013, 70 (20), pp.3753-3772. ⟨10.1007/s00018-013-1270-z⟩. ⟨hal-00867345⟩