Editorial [Hot Topic: ING Family of Tumor Suppressors (Guest Editor: Tatiana G. Kutateladze)]

The newly emerged Inhibitor of Growth (ING) family of tumor suppressors contains five evolutionary conserved members. The ING1-ING5 proteins are involved in numerous fundamental nuclear processes, including control of cell growth and DNA damage repair, cellular senescence and apoptosis. They also play a pivotal role in cancer development and progression, as the expression of ING proteins is often reduced or misregulated in human malignancies. Although mechanisms underlying the biological, physiological and tumorigenic activities of this family remain unclear, the recent studies have shed light on several important functions of the ING proteins. ING1-ING5 have been characterized as native subunits of large multiprotein histone deacetylase (HDAC) and histone acetyltransferase (HAT) complexes and are now viewed as essential regulators of chromatin acetylation. All five ING members contain a carboxy-terminal plant homeodomain (PHD) finger that recognizes histone H3 trimethylated at lysine 4, and unique amino-terminal regions that bind distinct components of the HDAC and HAT complexes. The ING proteins function as tethering molecules that stabilize the enzymatic complexes at chromatin to promote local histone acetylation or deacetylation and regulate gene expression. These properties of ING1-ING5 could bridge epigenetic control, transcriptional regulation and chromatin remodeling with neoplastic transformation. Various ING-mediated cellular processes are tightly linked to p53-dependent signaling pathways, and therefore ING1-ING5 may also act as tumor suppressors through altering the activity of p53. The specific interactions of the amino-terminal regions with other effectors, including Lamin A and PCNA, implicate the ING members in even more diverse biological processes that are associated with different forms of cancer. Thus, the ING proteins are engaged in multiple contacts with key players that collectively regulate a wide variety of cancer critical pathways. In this issue of Current Drug Targets we summarize the current knowledge of ING biology, highlight the remarkable progress recently made in understanding the tumorigenic activities of the ING family, and discuss the potential of using the ING proteins as biomarkers and/or targets for drug development.