p53 and RB Cooperate to Suppress Transposable Elements

Abstract

Accumulating data suggest that the long interspersed nuclear element 1 (LINE1), a major class of transposable elements, can promote tumorigenesis by causing deletions of tumor suppressor genes, amplifications of oncogenes, and chromosomal translocations(1). LINE1 and other transposable elements such as short interspersed nuclear elements (SINEs) can be activated during cancer development. Aberrant transposon expression has been correlated with loss of p53, however, how the loss of p53 or other tumor suppressors leads to activation of transposons during tumorigenesis remains to be fully understood. Here, we investigate the link between loss of the p53 and RB tumor suppressors and derepression of transposable elements. We observe that loss of p53 and RB in mouse embryonic fibroblasts leads to epigenetic changes, such as loss of DNA and histone methylation, which correlate with marked upregulation of LINE and SINE transposable elements. These results suggest that p53 and RB may utilize epigenetic mechanisms that work in tandem to suppress transposons, which may contribute to tumor suppression.

Naturally occurring T-cell-mediated antitumor immune response to LINE-1 antigens in mice that can be enhanced by vaccination and TLR5 agonist

“…L1 elements are transcriptionally silenced in most normal cells due to multiple mechanisms of epigenetic repression, including DNA methylation and chromatin modifications; the latter mechanism involves histone deacetylases (e.g., Sirtuin 6 6 ) tumor suppressors p53 7 and Rb 8,9 . L1 elements are frequently derepressed in tumors, contributing to cancer genome instability 10 based on the inherent potential of somatic L1 insertions to drive tumorigenesis by activating oncogenes or inactivating tumor suppressor genes 8 .…”