title: Defining the essential function of FBP/KSRP proteins: Drosophila Psi interacts with the mediator complex to modulate MYC transcription and tissue growth.
abstract: Despite two decades of research, the major function of FBP-family KH domain proteins during animal development remains controversial. The literature is divided between RNA processing and transcriptional functions for these single stranded nucleic acid binding proteins. Using Drosophila, where the three mammalian FBP proteins (FBP1-3) are represented by one ortholog, Psi, we demonstrate the primary developmental role is control of cell and tissue growth. Co-IP-mass spectrometry positioned Psi in an interactome predominantly comprised of RNA Polymerase II (RNA Pol II) transcriptional machinery and we demonstrate Psi is a potent transcriptional activator. The most striking interaction was between Psi and the transcriptional mediator (MED) complex, a known sensor of signaling inputs. Moreover, genetic manipulation of MED activity modified Psi-dependent growth, which suggests Psi interacts with MED to integrate developmental growth signals. Our data suggest the key target of the Psi/MED network in controlling developmentally regulated tissue growth is the transcription factor MYC. As FBP1 has been implicated in controlling expression of the MYC oncogene, we predict interaction between MED and FBP1 might also have implications for cancer initiation and progression.
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Linna
authors.initials: L
authors.lastname: Guo
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Olga
authors.initials: O
authors.lastname: Zaysteva
authors.affiliation: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Zuqin
authors.initials: Z
authors.lastname: Nie
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Naomi C
authors.initials: NC
authors.lastname: Mitchell
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jue Er
authors.initials: JE
authors.lastname: Amanda Lee
authors.affiliation: Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3010, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ware
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Parsons
authors.affiliation: Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3010, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Luwor
authors.affiliation: Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, VIC 3002, Australia.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Poortinga
authors.affiliation: Department of Medicine, St. Vincent's Hospital, University of Melbourne, Parkville, VIC 3010, Australia Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra City, ACT 2600, Australia.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
authors.affiliation: Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Levens
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia l.quinn@unimelb.edu.au.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Quinn
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D009024:Morphogenesis; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D016601:RNA-Binding Proteins; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D056892:Mediator Complex; D009687:Nuclear Proteins; C092281:PSI protein, Drosophila; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D012319:RNA Polymerase II