Abstract
Polycomb group proteins have long been linked to the occurrence of different forms of cancer. Polycomb proteins form at least two distinct complexes, the Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). Some of the PRC complex subunits have been found to be overexpressed in a variety of different tumors. Epigenetic perturbations are likely to be the cause for transcriptional misregulation of tumor suppressor genes and of certain cell fates. It is especially critical for stem cells that their potential to self-renewal and to differentiate is tightly controlled and properly orchestrated. Misregulation of Polycomb protein levels often leads to either a block or unscheduled activation of developmental pathways, thereby enhancing the proliferation capability of a cell. The consequences of this misregulation have been linked to the establishment of cancer stem cells, which can produce tumors through a combination of increased self-renewal and the lack of complete cellular differentiation. Cancer stem cells are believed to persist within tumors and to elicit relapse and metastasis. In this review, we recapitulate the roles of Polycomb proteins in stem cell biology, and the impact their misregulation can have on cancer.
Highlights
Polycomb proteins were initially identified in Drosophila melanogaster as genes important for developmental pathways
We have recently found that the ubiquitin residue has a functional role as a platform for transcriptional activation.[18]
PRC1 seems to block the transcriptional elongation of polymerase II (Pol II) at so-called bivalent genes, which are decorated with both repressive and activating trimethyl marks (H3K27me[3] and H3K4me[3], respectively; Figure 1).[19]
Summary
Polycomb group proteins have long been linked to the occurrence of different forms of cancer. Epigenetic perturbations are likely to be the cause for transcriptional misregulation of tumor suppressor genes and of certain cell fates It is especially critical for stem cells that their potential to self-renewal and to differentiate is tightly controlled and properly orchestrated. Misregulation of Polycomb protein levels often leads to either a block or unscheduled activation of developmental pathways, thereby enhancing the proliferation capability of a cell. The consequences of this misregulation have been linked to the establishment of cancer stem cells, which can produce tumors through a combination of increased self-renewal and the lack of complete cellular differentiation. Cell Death and Disease (2011) 2, e204; doi:10.1038/cddis.2011.84; published online 1 September 2011 Subject Category: Cancer
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