ING1

ING1 Full Name

inhibitor of growth family, member 1

ING1 Introduction

Inhibitor of growth family member 1 (ING1) is the founding member of the ING (inhibitor of growth) family of type II tumor suppressor proteins, which includes ING1 through ING5. Encoded by the ING1 gene on chromosome 13q34, a region frequently affected by loss of heterozygosity in human cancers, ING1 is a multifaceted nuclear protein that participates in the regulation of apoptosis, cell cycle progression, senescence, and DNA repair. Multiple ING1 isoforms are generated through alternative splicing (including p47ING1a, p33ING1b, and p24ING1c), with p33ING1b being the most extensively studied and widely expressed isoform. ING1 exerts its biological functions primarily as a stoichiometric component of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes.

Figure 1. Strcuture of ING1.

Chromatin Remodeling and p53-Dependent Tumor Suppression
ING1 functions as a core component of the Sin3A-HDAC and HBO1-HAT chromatin-modifying complexes through its highly conserved C-terminal plant homeodomain (PHD) finger, which binds with high specificity to histone H3 trimethylated at lysine 4 (H3K4me3), a mark characteristic of transcriptionally active chromatin. By reading this epigenetic mark, ING1 recruits HDAC activity to target gene promoters to facilitate transcriptional repression, or alternatively recruits HAT activity via HBO1 to promote transcriptional activation, depending on the cellular context and the specific complex assembled. A major facet of ING1 tumor suppression involves cooperation with the p53 tumor suppressor: following DNA damage, ING1 physically interacts with and stabilizes p53, enhancing p53 acetylation, promoting p53-dependent transactivation of target genes (e.g., p21/CDKN1A, BAX), and facilitating p53-mediated growth arrest or apoptosis. This functional cooperation positions ING1 as a critical accessory factor in the p53 tumor suppression network.

ING1 in Human Cancer, Cellular Senescence, and Prognostic Significance
ING1 expression is frequently downregulated or lost in a broad spectrum of human malignancies through multiple mechanisms including promoter hypermethylation, loss of heterozygosity at the 13q34 locus, and cytoplasmic mislocalization that sequesters ING1 away from its nuclear targets. Reduced ING1 expression has been documented in breast cancer, gastric cancer, head and neck squamous cell carcinoma, melanoma, and acute lymphoblastic leukemia, among others, and generally correlates with higher tumor grade, increased metastatic potential, and poor clinical prognosis. ING1 also promotes cellular senescence, an irreversible proliferative arrest that serves as a potent tumor-suppressive barrier, through its cooperation with p53 and pRb pathways. Restoration of ING1 expression in ING1-deficient cancer cell lines suppresses proliferation, induces apoptosis, and sensitizes cells to chemotherapeutic agents and ionizing radiation. These observations identify ING1 as a bona fide tumor suppressor and suggest that therapeutic strategies to restore or mimic ING1 function could have clinical utility across multiple cancer types. ING1 expression status is being evaluated as a prognostic and predictive biomarker to guide treatment decisions in oncology.

Alternate Names for ING1

ING1; inhibitor of growth family, member 1; inhibitor of growth protein 1; growth inhibitor ING1; growth inhibitory protein ING1; inhibitor of growth 1; p24ING1c; p33; p33ING1; p33ING1b; p47; p47ING1a; tumor suppressor ING1;