Inhibitor of growth tumor suppressors in cancer progression

Abstract

The inhibitor of growth (ING) family of tumor suppressors has five members and is implicated in the control of apoptosis, senescence, DNA repair, and cancer progression. However, little is known about ING activity in the regulation of cancer progression. ING members and splice variants seem to behave differently with respect to cancer invasion and metastasis. Interaction with histone trimethylated at lysine 4 (H3K4me3), hypoxia inducible factor-1 (HIF-1), p53, and nuclear factor kappa-B (NF-kappaB) are potential mechanisms by which ING members exert effects on invasion and metastasis. Subcellular mislocalization, rapid protein degradation, and to a lesser extent ING gene mutation are among the mechanisms responsible for inappropriate ING levels in cancer cells. The aim of this review is to summarize the different roles of ING family tumor suppressors in cancer progression and the molecular mechanisms involved.

Crosstalk between epigenetic readers regulates the MOZ/MORF HAT complexes

“…[43][44][45][46] In addition to being a core component of the MOZ/ MORF complexes, ING5 co-purifies with another major HAT complex, HBO1, which is responsible for acetylation of histone H4K5/K8/K12 and H3K14. 3,35,36 ING5 is a short, 240-residue protein that has an N-terminal (ING) region involved in the interactions with other proteins including BRPF1/2/3, and a single reader, the PHD finger specific for H3K4me3 (Fig.…”

“…32 Another subunit of the MOZ/ MORF complexes, ING5 is downregulated or mutated in various human malignancies, including head and neck squamous cell, gastric, colorectal, and oral squamous cell carcinomas. [43][44][45][46][69][70][71] Thus, the core components of the MOZ/MORF complexes represent attractive drug targets as translocations, mutations, and dysregulation of these components are linked to cancer and developmental diseases. The structural insight into the reader-ligand interactions and the interplay between the readers within the MOZ/MORF complexes offer new tools in the development of therapeutics to treat diseases caused by aberrant acetylation.…”

Conserved Molecular Interactions within the HBO1 Acetyltransferase Complexes Regulate Cell Proliferation

“…Their homology is highest at the carboxyl termini within a plant homeodomain (PHD) finger-a motif common to many chromatin regulatory proteins (8, 54). Expression analyses of several tumor types show that ING genes are either mutated or downregulated in many forms of cancer (43,73), and a number of studies have implicated the ING proteins in the regulation of the cell cycle and proliferation, cellular aging and senescence, hormone signaling pathways, brain tumor growth, and angiogenesis (reviewed in reference 51). These functions stem from direct mechanistic roles in chromatin modification and remodeling, gene-specific transcription regulation, and DNA repair, recombination, and replication (2, 54, 61).…”

Regulation of p53 by ING family members in suppression of tumor initiation and progression

“…Notably, mutations or aberrant expression of ING family members have been frequently observed in various malignancies [40,[66][67][68][69][70][71][72][73] implying their involvement in various aspects of cancer biology. In the next section, we will briefly highlight the most prominent functions of ING proteins.…”