title: SCF(Slmb) E3 ligase-mediated degradation of Expanded is inhibited by the Hippo pathway in Drosophila.
abstract: Deregulation of the evolutionarily conserved Hippo pathway has been implicated in abnormal development of animals and in several types of cancer. One mechanism of Hippo pathway regulation is achieved by controlling the stability of its regulatory components. However, the executive E3 ligases that are involved in this process, and how the process is regulated, remain poorly defined. In this study, we identify, through a genetic candidate screen, the SCF(Slmb) E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues via mediation of the degradation of Expanded (Ex). Mechanistic study shows that Slmb-mediated degradation of Ex is inhibited by the Hippo signaling. Considering the fact that Hippo signaling suppresses the transcription of ex, we propose that the Hippo pathway employs a double security mechanism to ensure fine-tuned homeostasis during development.
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Chuanxian
authors.initials: C
authors.lastname: Wei
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Dai
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Wu
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dui
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida 32304-4295, USA.
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
authors.affiliation: 1] State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China [2] Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Dongfengxi Road 195, Guangzhou, Guangdong 510182, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D060066:Protein Interaction Maps; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044843:SKP Cullin F-Box Protein Ligases; C085090:ex protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases