title: The Drosophila F-box protein Slimb controls dSmurf protein turnover to regulate the Hippo pathway.
abstract: SMAD ubiquitination regulatory factors 1 and 2 (Smurf1/2) are members of the HECT domain E3 ligase family which play crucial roles in the regulation of cell cycle progression, planar cell polarity, cancer metastasis and cell apoptosis. We recently showed that the Drosophila homolog dSmurf controls the stability of Warts kinase to regulate the Hippo pathway. In the current study, we found that the F-box protein Slimb controls dSmurf protein level to regulate the Hippo pathway. Slimb physically associates with dSmurf as revealed by co-immunoprecipitation assay in S2 cells. The C-terminal WD40 repeats of Slimb (188-510 amino acid) and the C-terminal HECT domain of dSmurf (723-1061 amino acid) are necessary for their binding. Interaction with Slimb leads to the ubiquitination and degradation of dSmurf, resulting in negative regulation of dSmurf-mediated Yki phosphorylation and activity in the Hippo pathway. Thus our study revealed a new regulatory mechanism of the Hippo pathway which may provide implications for developing tumor treatment.
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Liangchang
authors.initials: L
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Runan
authors.initials: R
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Science; Nankai University; Tianjin, PR China. Electronic address: wusa@nankai.edu.cn.
authors.forename: Shian
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D044783:F-Box Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D057149:Ubiquitinated Proteins; C110233:slmb protein, Drosophila; C492378:Smurf protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Hippo signaling; Slimb; Ubiquitination; dSmurf