title: The Hippo kinase promotes Scalloped cytoplasmic localization independently of Warts in a CRM1/Exportin1-dependent manner in Drosophila.
abstract: Scalloped (SD) is a transcription factor characterized by a TEA/ATTS DNA binding domain. To activate transcription, SD must interact with its coactivators, including Yorkie (YKI) or Vestigial (VG). YKI is the downstream effector of the Hippo signaling pathway that plays a key role in the control of tissue growth. The core components of this pathway are two kinases, Hippo (HPO) and Warts (WTS), which negatively regulate the activity of the SD/YKI complex, retaining YKI in the cytoplasm. We previously showed that HPO kinase can also reduce SD/VG transcriptional activity in Drosophila S2 cells. We further investigated the relationship between the SD/VG complex and the Hippo pathway. We show here that HPO overexpression suppresses overgrowth induced by SD/VG in vivo during Drosophila development. Using S2 cells, we show that HPO promotes the translocation of SD to the cytoplasm in a CRM1-dependent manner, thereby inhibiting the induction of SD/VG target genes. Using RNAi-mediated depletion of yki and a mutant SD protein unable to interact with YKI, we demonstrate that HPO regulates SD localization independently of YKI. This function requires HPO kinase activity, yet surprisingly, not its downstream effector kinase WTS. Taken together, these observations reveal a new and unexpected role of HPO kinase in the regulation of a transcription factor independently of YKI.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molecular Oncology Team, Institut Jacques Monod, Unité Mixte de Recherche 7592, Centre National de Recherche Scientifique (CNRS), Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Cagliero
authors.forename: Antoine
authors.initials: A
authors.lastname: Forget
authors.forename: Enrico
authors.initials: E
authors.lastname: Daldello
authors.forename: Joël
authors.initials: J
authors.lastname: Silber
authors.forename: Alain
authors.initials: A
authors.lastname: Zider
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014860:Warts / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D017346:Protein Serine-Threonine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C087984:sd protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases