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 influencing 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 INhibitor of Growth (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 specifically 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 deregulated or mislocalized in various cancer types and certain ING variants are upregulated in replicative senescence, affecting epigenetic mechanisms and altering chromatin structure. The ing gene that is best studied, ing1, encodes two major splicing variants that encode ING1a, a regulator of cell senescence, and ING1b, a protein that promotes apoptosis. In this chapter, we provide an overview of the domains of the ING proteins, descriptions of the processes affected by the INGs and describe in more detail their functions in cancer and cell aging. Those characteristics of the INGs that allow them to impact both processes are highlighted.
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Acknowledgements
We apologize to our colleagues for the many relevant papers we were unable to cite due to length constraints. UMT is a recipient of an Alberta Cancer Foundation (ACF) graduate award and KR holds a Scientist Award from Alberta Innovates-Health Solutions (AI-HS). This work was supported by grants from AI-HS and the Canadian Breast Cancer Foundation.
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Tran, U.M., Rajarajacholan, U., Riabowol, K. (2014). Function of the ING Proteins in Cancer and Senescence. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 2. Tumor Dormancy and Cellular Quiescence and Senescence, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7726-2_18
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