Inhibitor of growth-4 mediates chromatin modification and has a suppressive effect on tumorigenesis and innate immunity.

Inhibitor of growth-4 (ING4) is a member of the ING family and acts as a tumor suppressor protein. ING4 is a promising candidate for cancer research due to its anti-angiogenic function and its role in the inhibition of cell migration, cell cycle, and induction of apoptosis. Interaction of this protein with the histone acetyl transferase complex plays a vital role in the regulation of multiple nuclear factor kappa light chain enhancer of activated B cells response elements and thus in the regulation of innate immunity. Splice variants of ING4 have different binding affinities to target sites, which results in the enhancement of its functional diversity. ING4 is among the few known regulatory proteins that can directly interact with chromatin as well as with transcription factors. The influence of ING4 on tumor necrosis factor-α, keratinocyte chemoattractant, interleukin (IL)-6, IL-8, matrix metalloproteinases, cyclooxygenase-2, and IκBα expression clearly demonstrates its critical role in the regulation of inflammatory mediators. Its interaction with liprin α1 and p53 contribute to mitigate cell spreading and induce apoptosis of cancer cells. Multiple factors including breast cancer melanoma suppressor-1 are upstream regulators of ING4 and are frequently deactivated in tumor cells. In the present review, the different properties of ING4 are discussed, and its activities are correlated with different aspects of cell physiology. Special emphasis is placed on our current understanding of ING4 with respect to its influence on chromatin modification, tumorigenesis, and innate immunity.