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The mitotic checkpoint gene, SIL is regulated by E2F1
Author(s) -
Erez Ayelet,
Chaussepied Marie,
Castiel Asher,
ColaizzoAnas Tina,
Aplan Peter D.,
Ginsberg Doron,
Izraeli Shai
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23665
Subject(s) - e2f , mitosis , biology , chromatin immunoprecipitation , ectopic expression , gene silencing , microbiology and biotechnology , cancer research , small hairpin rna , gene knockdown , cell cycle , gene expression , gene , promoter , genetics
The SIL gene expression is increased in multiple cancers and correlates with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. SIL regulates mitotic entry, organization of the mitotic spindle and cell survival. The E2F transcription factors regulate cell cycle progression by controlling the expression of genes mediating the G1/S transition. More recently, E2F has been shown to regulate mitotic spindle checkpoint genes as well. As SIL expression correlates with mitotic checkpoint genes, we hypothesized that SIL is regulated by E2F. We mined raw data of published experiments and performed new experiments by modification of E2F expression in cell lines, reporter assays and chromatin immunoprecipitation. Ectopic expression or endogenous activation of E2F induced the expression of SIL, while knockdown of E2F by shRNA, downregulated SIL expression. E2F activated SIL promoter by reporter assay and bound to SIL promoter in vivo . Taken together these data demonstrate that SIL is regulated by E2F. As SIL is essential for mitotic entry, E2F may regulate G2/M transition through the induction of SIL. Furthermore, as silencing of SIL cause apoptosis in cancer cells, these finding may have therapeutic relevance in tumors with constitutive activation of E2F. Published 2008 Wiley‐Liss, Inc.