Inhibitor of growth family member 4 (ING4)

Inhibitor of growth family member 4 (ING4) is a critical tumor suppressor protein belonging to the ING family, characterized by a conserved plant homeodomain (PHD) finger that acts as an epigenetic reader of H3K4me3 marks [1, 4]. By recruiting histone acetyltransferase (HAT) complexes like HBO1, ING4 facilitates chromatin remodeling and regulates the expression of genes involved in cell cycle control and genomic stability [4, 7]. Biologically, ING4 induces G1-phase cell cycle arrest and promotes apoptosis through both intrinsic and extrinsic pathways, while also serving as a potent inhibitor of tumor angiogenesis by suppressing pro-angiogenic factors such as NF-kappaB, HIF-1alpha, and IL-8 [1, 6, 12]. In many human cancers, including glioblastoma, breast, and colorectal cancer, ING4 is frequently downregulated or deleted, which correlates with increased metastasis and poor prognosis [1, 10, 12]. Therapeutic strategies are currently focused on restoring ING4 function through adenovirus-mediated gene therapy or developing small molecule modulators to enhance its tumor-suppressive activity and sensitize cancer cells to conventional treatments [2, 3, 6]. Beyond oncology, ING4 has also been implicated in regulating inflammatory responses and fibrosis, suggesting a broader role in maintaining cellular homeostasis [1, 6]. Its interaction with key transcription factors like p53 and NF-kappaB makes it a central node in the cellular response to stress and oncogenic signals [1, 11].

Other names

p29ING4my036Brain my036 proteinCandidate tumor suppressor p33 ING1 homolog

Inhibitor of growth family member 4 (ING4) functions as an epigenetic reader by binding to trimethylated lysine 4 on histone H3 (H3K4me3) via its plant homeodomain (PHD) finger [1, 4]. This binding allows ING4 to recruit histone acetyltransferase (HAT) complexes, such as HBO1, to specific genomic regions to regulate gene transcription [7, 11]. ING4 suppresses tumor progression by physically interacting with the p65 subunit of NF-kappaB to inhibit its transcriptional activity and by interacting with HIF prolyl hydroxylase 2 (HPH-2) to suppress hypoxia-inducible factor (HIF) activity [1, 6, 11]. Additionally, it enhances p53-mediated transcription by promoting p53 acetylation through its interaction with the acetyltransferase p300 [1, 11].