E2F6: a member of the E2F family that does not modulate squamous differentiation.
The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members.
Epithelial Pathobiology Group, Cancer Biology Programme, Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
Chung Fai
CF
Wong
Liam M
LM
Barnes
Louise
L
Smith
Claudia
C
Popa
Magdalena M
MM
Serewko-Auret
Nicholas A
NA
Saunders
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D004396:Coloring Agents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D050701:E2F6 Transcription Factor; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014162:Transfection
D004396:Coloring Agents; D018076:DNA, Complementary; D050701:E2F6 Transcription Factor; C491744:E2F6 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D001973:Bromodeoxyuridine