Hfp inhibits Drosophila myc transcription and cell growth in a TFIIH/Hay-dependent manner
Naomi C Mitchell, Timothy M Johanson, Nicola J Cranna, Amanda Lee Jue Er, Helena E Richardson, Ross D Hannan, Leonie M Quinn
DEVELOPMENT | COMPANY OF BIOLOGISTS LTD | Published : 2010
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..View full abstract
We thank Mario Zurita for the anti-Hay and Julie Secombe and Bob Eisenman for anti-dMyc antibodies; Gretchen Poortinga for helping develop the ChIP experiments in Drosophila; Ben Britten Smith for developing image analysis software; Peter Burke for help with injection of the UAS-hay transgene; and Nancy Reyes and the IMVS animal house for preparation of the Hfp antibody. This work was supported by the Australian National Health and Medical Research Council (NHMRC) and Cancer Council Victoria (CCV). L. M. Q. and N.C.M. are supported by an NHMRC project grant. H. E. R. and R. D. H. both hold Senior NHMRC Fellowships. N.J.C. is supported by an Australian Postgraduate Award (APA).