Figure 3.

A simplified schematic highlighting the non-canonical roles of p27 in stem-cell biology and metastasis. Nuclear p27 regulates differentiation in various cell types. p27 levels are low in mouse and human embryonic stem cells (mESCs and hESCs) and it markedly increases as these cells are induced to differentiate. (a) p27 contributes to transcriptional repression of SOX2, a pluripotency gene, during differentiation of pluripotent cells and in differentiated cells by associating with the SOX2-SRR2 enhancer together with the repressive complex p130-E2F4-SIN3A. (b) In differentiating pluripotent cells p27 associates with Brachyury and Twist1 promoters to repress the transcription of these genes; the identity of the repressor complex that p27 associates with on these promoters remains to be defined. (c) Neurogenin2 (Ngn2) is a proneural basic helix-loop-helix transcription factor that plays a central role in the neuronal differentiation of cortical progenitors. p27 plays a key role in this process by stabilizing the neurogenin2 protein in a CDK-independent manner. (d) Cytoplasmic p27 contributes to tumorigenesis and metastasis by exerting influence on various processes such as expansion of the stem cell pool, cell migration and invasion, and epithelial-mesenchymal transition (see text for details).