Hfp inhibits Drosophila myc transcription and cell growth in a TFIIH/Hay-dependent manner.
An unresolved question regarding the RNA-recognition motif (RRM) protein Half pint (Hfp) has been whether its tumour suppressor behaviour occurs by a transcriptional mechanism or via effects on splicing. The data presented here demonstrate that Hfp achieves cell cycle inhibition via an essential role in the repression of Drosophila myc (dmyc) transcription. We demonstrate that regulation of dmyc requires interaction between the transcriptional repressor Hfp and the DNA helicase subunit of TFIIH, Haywire (Hay). In vivo studies show that Hfp binds to the dmyc promoter and that repression of dmyc transcription requires Hfp. In addition, loss of Hfp results in enhanced cell growth, which depends on the presence of dMyc. This is consistent with Hfp being essential for inhibition of dmyc transcription and cell growth. Further support for Hfp controlling dmyc transcriptionally comes from the demonstration that Hfp physically and genetically interacts with the XPB helicase component of the TFIIH transcription factor complex, Hay, which is required for normal levels of dmyc expression, cell growth and cell cycle progression. Together, these data demonstrate that Hfp is crucial for repression of dmyc, suggesting that a transcriptional, rather than splicing, mechanism underlies the regulation of dMyc and the tumour suppressor behaviour of Hfp.
Mitchell
Naomi C
NC
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Melbourne, Australia.
Johanson
Timothy M
TM
Cranna
Nicola J
NJ
Er
Amanda Lee Jue
AL
Richardson
Helena E
HE
Hannan
Ross D
RD
Quinn
Leonie M
LM
D020121:5' Untranslated Regions; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D049109:Cell Proliferation; D004265:DNA Helicases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D017344:Genes, Insect; D016259:Genes, myc; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D016196:S Phase; D015398:Signal Transduction; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
D020121:5' Untranslated Regions; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; C484363:Hfp protein, Drosophila; C102284:Myc protein, Drosophila; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; C078672:hay protein, Drosophila; D004265:DNA Helicases