Abstract
The proteins belonging to the inhibitor of growth (ING) family of proteins serve as epigenetic readers of the H3K4Me3 histone mark of active gene transcription and target histone acetyltransferase (HAT) or histone deacetylase (HDAC) protein complexes, in order to alter local chromatin structure. These multidomain adaptor proteins interact with numerous other proteins to facilitate their localization and the regulation of numerous biochemical pathways that impinge upon biological functions. Knockout of some of the ING genes in murine models by various groups has verified their status as tumor suppressors, with ING1 knockout resulting in the formation of large clear-cell B-lymphomas and ING2 knockout increasing the frequency of ameloblastomas, among other phenotypic effects. ING4 knockout strongly affects innate immunity and angiogenesis, and INGs1, ING2, and ING4 have been reported to affect apoptosis in different cellular models. Although ING3 and ING5 knockouts have yet to be published, preliminary reports indicate that ING3 knockout results in embryonic lethality and that ING5 knockout may have postpartum effects on stem cell maintenance. In this review, we compile the known information on the domains of the INGs and the effects of altering ING protein expression, to better understand the functions of this adaptor protein family and its possible uses for targeted cancer therapy.
Highlights
In the last decade, thanks largely to advancements in sequencing and array technologies, there has been significant progress in understanding the role of the epigenome in human diseases, including cancer [1,2,3]
We explore what is known regarding the functions of the inhibitor of growth family of proteins (ING1–ING5), which plays key roles in regulating histone acetylation through the recruitment of different histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes to lysine residues in nucleosomes that are marked by methylation
It was suggested that the spermatogenesis defect caused by ING2 deficiency could be due to the disruption of stage-specific histone modifications, similar to what happens to SIRT1 knockout animals
Summary
Thanks largely to advancements in sequencing and array technologies, there has been significant progress in understanding the role of the epigenome in human diseases, including cancer [1,2,3]. Lysine methylation has a wide range of possible effects on gene expression, and it varies according to the residues being methylated This modification can lead to either the activation or repression of transcription. The addition of an acetyl group to the histone tails, like methylation, helps to neutralize the positive charge on lysine and loosens its interaction with DNA, opening up chromatin, which allows for the recruitment of chromatin remodelers and transcription factors, and usually increases gene expression [16]. We explore what is known regarding the functions of the inhibitor of growth family of proteins (ING1–ING5), which plays key roles in regulating histone acetylation through the recruitment of different HAT and HDAC complexes to lysine residues in nucleosomes that are marked by methylation
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