The mitotic checkpoint gene, SIL is regulated by E2F1.
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.
Erez
Ayelet
A
Department of Pediatric Hemato-Oncology and the Sheba Cancer Research Center, Tel-Hashomer, Israel.
Chaussepied
Marie
M
Castiel
Asher
A
Colaizzo-Anas
Tina
T
Aplan
Peter D
PD
Ginsberg
Doron
D
Izraeli
Shai
S
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004331:Drosophila melanogaster; D050687:E2F1 Transcription Factor / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008938:Mitosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D017931:DNA Primers; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C071236:STIL protein, human