PMID- 19900439 OWN - NLM STAT- MEDLINE DCOM- 20100225 LR - 20231213 IS - 1095-564X (Electronic) IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 337 IP - 2 DP - 2010 Jan 15 TI - Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. PG - 303-12 LID - 10.1016/j.ydbio.2009.10.046 [doi] AB - The Hippo (Hpo) signaling pathway controls cell growth, proliferation and apoptosis in both Drosophila and vertebrates. In Drosophila, Hpo signaling regulates gene expression by inhibiting a transcription complex consisting of the transcriptional coactivator Yorkie (Yki) and the TEAD/TEF family of transcription factor Scalloped (Sd). Here we provide genetic evidence that both isoforms of 14-3-3, 14-3-3varepsilon and 14-3-3zeta, regulate Yki activity through modulating its subcellular localization. Inactivation of 14-3-3 by RNAi or genetic mutations enhanced whereas overexpression of 14-3-3 suppressed tissue overgrowth induced by Yki overexpression. Loss of 14-3-3 resulted in the accumulation of Yki in the nucleus. We found that regulation of Yki by 14-3-3 was mediated by phosphorylation of Yki at S168. In addition, we found that Hpo signaling also inhibited Yki nuclear localization and activity by phosphorylating Yki at S111 and S250, and this inhibition appears to be independent of 14-3-3. Finally, we provided evidence that Hpo signaling restricted Yki nuclear localization depending on CRM1-mediated nuclear export. CI - Copyright 2009 Elsevier Inc. All rights reserved. FAU - Ren, Fangfang AU - Ren F AD - Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. FAU - Zhang, Lei AU - Zhang L FAU - Jiang, Jin AU - Jiang J LA - eng GR - R01 GM067045/GM/NIGMS NIH HHS/United States GR - R01 GM067045-06/GM/NIGMS NIH HHS/United States GR - R01 GM061269-09/GM/NIGMS NIH HHS/United States GR - R01 GM067045-07/GM/NIGMS NIH HHS/United States GR - GM067045/GM/NIGMS NIH HHS/United States GR - GM061269/GM/NIGMS NIH HHS/United States GR - R01 GM061269-08/GM/NIGMS NIH HHS/United States GR - R01 GM061269/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20091106 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (14-3-3 Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Karyopherins) RN - 0 (Nuclear Proteins) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Trans-Activators) RN - 0 (YAP-Signaling Proteins) RN - 0 (Yki protein, Drosophila) RN - 17885-08-4 (Phosphoserine) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (hpo protein, Drosophila) SB - IM MH - 14-3-3 Proteins/*metabolism MH - Active Transport, Cell Nucleus MH - Animals MH - Cell Nucleus/*metabolism MH - Drosophila Proteins/antagonists & inhibitors/*metabolism MH - Drosophila melanogaster/cytology/growth & development/*metabolism MH - Eye/cytology/growth & development MH - Gene Knockdown Techniques MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Karyopherins/metabolism MH - Nuclear Proteins/antagonists & inhibitors/*metabolism MH - Phosphorylation MH - Phosphoserine/metabolism MH - Protein Isoforms/metabolism MH - Protein Serine-Threonine Kinases/*metabolism MH - Protein Transport MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - *Signal Transduction MH - Subcellular Fractions/metabolism MH - Trans-Activators/antagonists & inhibitors/*metabolism MH - YAP-Signaling Proteins MH - Exportin 1 Protein PMC - PMC2812623 MID - NIHMS158704 EDAT- 2009/11/11 06:00 MHDA- 2010/02/26 06:00 PMCR- 2011/01/15 CRDT- 2009/11/11 06:00 PHST- 2009/08/06 00:00 [received] PHST- 2009/10/13 00:00 [revised] PHST- 2009/10/31 00:00 [accepted] PHST- 2009/11/11 06:00 [entrez] PHST- 2009/11/11 06:00 [pubmed] PHST- 2010/02/26 06:00 [medline] PHST- 2011/01/15 00:00 [pmc-release] AID - S0012-1606(09)01340-2 [pii] AID - 10.1016/j.ydbio.2009.10.046 [doi] PST - ppublish SO - Dev Biol. 2010 Jan 15;337(2):303-12. doi: 10.1016/j.ydbio.2009.10.046. Epub 2009 Nov 6.