The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila

被引:270
作者
Baumgartner, Roland [1 ]
Poernbacher, Ingrid [1 ]
Buser, Nathalie [1 ]
Hafen, Ernst [1 ]
Stocker, Hugo [1 ]
机构
[1] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland
关键词
TUMOR-SUPPRESSOR PATHWAY; ORGAN SIZE CONTROL; CELL CONTACT INHIBITION; IMAGINAL DISC GROWTH; PROLIFERATION ARREST; SIGNALING PATHWAYS; TEAD/TEF FAMILY; CYCLE EXIT; APOPTOSIS; FAT;
D O I
10.1016/j.devcel.2009.12.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.
引用
收藏
页码:309 / 316
页数:8
相关论文
共 37 条
[1]  
BADOUEL C, 2009, CELL, V16, P411
[2]   Yorkie and Scalloped: Partners in growth activation [J].
Bandura, Jennifer L. ;
Edgar, Bruce A. .
DEVELOPMENTAL CELL, 2008, 14 (03) :315-316
[3]   Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway [J].
Bennett, F. Christian ;
Harvey, Kieran F. .
CURRENT BIOLOGY, 2006, 16 (21) :2101-2110
[4]   The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane [J].
Chishti, AH ;
Kim, AC ;
Marfatia, SM ;
Lutchman, M ;
Hanspal, M ;
Jindal, H ;
Liu, SC ;
Low, PS ;
Rouleau, GA ;
Mohandas, N ;
Chasis, JA ;
Conboy, JG ;
Gascard, P ;
Takakuwa, Y ;
Huang, SC ;
Benz, EJ ;
Bretscher, A ;
Fehon, RG ;
Gusella, AF ;
Ramesh, V ;
Solomon, F ;
Marchesi, VT ;
Tsukita, S ;
Tsukita, S ;
Arpin, M ;
Louvard, D ;
Tonks, NK ;
Anderson, JM ;
Fanning, AS ;
Bryant, PJ ;
Woods, DF ;
Hoover, KB .
TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (08) :281-282
[5]   Delineation of a Fat tumor suppressor pathway [J].
Cho, Eunjoo ;
Feng, Yongqiang ;
Rauskolb, Cordelia ;
Maitra, Sushmita ;
Fehon, Rick ;
Irvine, Kenneth D. .
NATURE GENETICS, 2006, 38 (10) :1142-1150
[6]   A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila [J].
Dietzl, Georg ;
Chen, Doris ;
Schnorrer, Frank ;
Su, Kuan-Chung ;
Barinova, Yulia ;
Fellner, Michaela ;
Gasser, Beate ;
Kinsey, Kaolin ;
Oppel, Silvia ;
Scheiblauer, Susanne ;
Couto, Africa ;
Marra, Vincent ;
Keleman, Krystyna ;
Dickson, Barry J. .
NATURE, 2007, 448 (7150) :151-U1
[7]   From cell structure to transcription: Hippo forges a new path [J].
Edgar, BA .
CELL, 2006, 124 (02) :267-273
[8]   Protein interaction mapping:: A Drosophila case study [J].
Formstecher, E ;
Aresta, S ;
Collura, V ;
Hamburger, A ;
Meil, A ;
Trehin, A ;
Reverdy, C ;
Betin, V ;
Maire, S ;
Brun, C ;
Jacq, B ;
Arpin, M ;
Bellaiche, Y ;
Bellusci, S ;
Benaroch, P ;
Bornens, M ;
Chanet, R ;
Chavrier, P ;
Delattre, O ;
Doye, V ;
Fehon, R ;
Faye, G ;
Galli, T ;
Girault, JA ;
Goud, B ;
de Gunzburg, J ;
Johannes, L ;
Junier, MP ;
Mirouse, V ;
Mukherjee, A ;
Papadopoulo, D ;
Perez, F ;
Plessis, A ;
Rossé, C ;
Saule, S ;
Stoppa-Lyonnet, D ;
Vincent, A ;
White, M ;
Legrain, P ;
Wojcik, J ;
Camonis, J ;
Daviet, L .
GENOME RESEARCH, 2005, 15 (03) :376-384
[9]   Kibra Is a Regulator of the Salvador/Warts/Hippo Signaling Network [J].
Genevet, Alice ;
Wehr, Michael C. ;
Brain, Ruth ;
Thompson, Barry J. ;
Tapon, Nicolas .
DEVELOPMENTAL CELL, 2010, 18 (02) :300-308
[10]   SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila [J].
Goulev, Youlian ;
Fauny, Jean Daniel ;
Gonzalez-Marti, Beatriz ;
Flagiello, Domenico ;
Silber, Joeel ;
Zider, Alain .
CURRENT BIOLOGY, 2008, 18 (06) :435-441