E2F1 up-regulates the expression of the tumour suppressor axin2 both by activation of transcription and by mRNA stabilisation.
Axin2 is a negative regulator of Wnt/beta-catenin signalling with roles in early development and tumour suppression. Axin2 is induced by E2F1 and therefore acts as a point of cross-talk between the pRb/E2F and Wnt/beta-catenin pathways: two of the most frequently deregulated pathways in human cancers. In this study, we show that E2F1 up-regulates axin2 by two independent mechanisms. The human axin2 gene allows transcription of messages with three different 5' untranslated regions and in the first mechanism E2F1 directly activates the transcription of only one of these species by acting at canonical E2F binding sites. Second, E2F1 induces stabilisation of axin2 mRNAs. We discuss this regulation with respect to other known E2F targets.
Hughes
Thomas A
TA
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, UK. t.hughes@ich.ucl.ac.uk
Brady
Hugh J M
HJ
D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D060466:Axin Protein; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005091:Exons / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
D020121:5' Untranslated Regions; C491761:AXIN2 protein, human; D060466:Axin Protein; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors