Hfp, the Drosophila homolog of the mammalian c-myc transcriptional-repressor and tumor suppressor FIR, inhibits dmyc transcription and cell growth.
Here we highlight our recent study, which revealed a mechanism critical for tight regulation of Drosophila myc (dmyc) transcription. Our previous work demonstrated that the RRM (RNA recognition motif) protein Half pint (Hfp) behaves as a growth and cell cycle inhibitor and work from D. Levens group has shown the mammalian ortholog, FIR (the FBP Interacting Repressor), is a tumor suppressor. Although RRM domain containing proteins such as Hfp and FIR have been ascribed splicing and transcriptional roles, our work suggests that Hfp is likely to achieve cell cycle inhibition via direct repression of dmyc transcription. We have demonstrated that Hfp binds to the dmyc promoter and is essential for repression of dmyc transcription, which requires interaction between Hfp and the DNA helicase subunit of Transcription Factor IIH (TFIIH), Haywire (Hay). Consistent with the increased levels of dmyc transcription, loss of Hfp makes cells overgrow in a manner dependent on the presence of dMyc. Thus our work has demonstrated that Hfp is critical for repression of dmyc and suggested a transcriptional, rather than splicing, mechanism underlies the ability of Hfp to regulate dMyc and function as a tumor suppressor. Thus we have extended knowledge from previous mammalian studies by providing in vivo evidence that the FIR homolog Hfp is required for repression of dmyc transcription, suggesting the mechanism proposed for repression of c-myc transcription by the mammalian RRM protein FIR is conserved in Drosophila.
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia.
Nicola J
NJ
Cranna
Naomi C
NC
Mitchell
Ross D
RD
Hannan
Leonie M
LM
Quinn
D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
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; D012319:RNA Polymerase II