ING Proteins: Tumour Suppressors or Oncoproteins

SIMPLE SUMMARY: The INhibitor of Growth (ING) family of proteins was founded when in 1996 ING1 was identified as a tumour suppressor, a protein that prevents cancer development. Important subsequent genetic and biochemical work in different models, showed that most ING family members are actually required for cellular proliferation, a hallmark of cancer cells. Although several studies suggest that INGs are broadly lost in cancer, some ING family members are amplified and correlate with a bad prognosis. This is especially true in hormone-dependent cancers, such as breast and prostate tumours. Herein, we review these studies and propose that ING proteins are not all tumour suppressors, but can play opposite role. Unquestionably, INGs have various functions, likely many yet to be discovered, and play complex roles during cancer development. ABSTRACT: The INhibitor of Growth family was defined in the mid-1990s by the identification of a tumour suppressor, ING1, and subsequent expansion of the family based essentially on sequence similarities. However, later work and more recent investigations demonstrate that at least a few ING proteins are actually required for normal proliferation of eukaryotic cells, from yeast to human. ING proteins are also part of a larger family of chromatin-associated factors marked by a plant homeodomain (PHD), which mediates interactions with methylated lysine residues. Herein, we discuss the role of ING proteins and their various roles in chromatin signalling in the context of cancer development and progression.