Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

Table 1

Factors influencing EWS-FLI1 activity and/or expression.

Posttranslational modifications
Phosphorylation	DNA binding, response to DNA damage and mitogens	[9–11]
Glycosylation	Transcriptional activation, cell growth, link with IGF-1 signaling	[12–14]
Direct protein-protein interactions
RNA polymerase II	Basal transcription machinery	[15]
hsRBP7	Basal transcription machinery	[16–18]
Creb-binding protein (CBP)/p300	Basal transcription machinery, regulation of EWS-FLI1 targets like p21 or MMP-1	[19–21]
RNA helicase A (RHA)	Modulator of transcription	[22]
BARD1	Putative tumor suppressor; genome surveillance, DNA repair and checkpoint control	[23]
FOS-JUN dimers	Binding to AP1 sequences synergizing with EWS-FLI1, regulation of uridine phosphorylase	[24]
NR0B1	Transcriptional regulator downstream of EWS-FLI1	[25]
small nuclear ribonucleoprotein (snRNP) U1C	pre-mRNA splicing	[26]
EWS	Functional consequences of this heterodimerization unknown	[20]
Factors indirectly affecting EWS-FLI1 activity
p53 and INK4A pathways	Loss of each one stabilizes EWS-FLI1	[27–33]
Hypoxia	Apoptosis resistance via HIF, chemotherapy failure, angiogenesis	[34–37]
IGF-1/IGF-1R pathway	EWS-FLI1 mediated cellular transformation, proliferation and survival	[38–45]
bFGF	Triggers EWS-FLI1 expression in serum-depleted ESFT cells	[46]
BLCAP	Ectopic overexpression decreases EWS-FLI1, apoptosis	[47]
miRNAs
miR-145	EWS-FLI1 repressed miRNA, regulatory feedback loop	[48, 49]
miR-100, miR-125b, miR-22, miR-221/222, miR-271 and miR29a	EWS-FLI1 repressed miRNAs, targets in IGF signalling pathway	[50]
let-7 family	EWS-FLI1 repressed miRNA, let 7-a is a direct target of EWS-FLI1	[51]
miRNA 17–92 cluster	EWS-FLI1 induced miRNAs	[51]