Function of the ING Proteins in Cancer and Senescence

Abstract

Age is one of the strongest correlates to the incidence of cancers known, suggesting that the two processes are linked. Cell aging (senescence) is increasingly being linked to epigenetic pathways, many of which have recently been found to be markedly altered in precancerous and cancer cells. Thus, misregulation of epigenetic pathways may impact both cancer and aging by infl uencing genetic and biochemical pathways common to both processes. Similar to the p53 and retinoblastoma (Rb) tumor suppressors that affect chromatin structure by genetic and epigenetic mechanisms, the IN hibitor of G rowth (ING) type II tumour suppressors affect pathways that contribute to cell aging and cancer. In particular, the INGs have been demonstrated to act as readers of the histone code by virtue of interacting specifi cally with the histone H3 residue H3K4Me3 and as targeting subunits of the writers of the histone code by being stoichiometric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. The ING proteins are frequently

ING4 Inhibits Proliferation and Induces Apoptosis in Human Melanoma A375 Cells via the Fas/Caspase-8 Apoptosis Pathway

“…Several studies demonstrated that INGs could enhance apoptosis via the death receptor-mediated extrinsic pathway (Fas/caspase-8 apoptosis pathway) in different cancers [19,20]. Our in vitro and in vivo data indicate that ING4 overexpression could increase the expression of Fas, an important member of the tumor necrosis factor receptor superfamily, which is involved in apoptosis.…”