dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development.
MAD plays an important role in decapentaplegic (DPP) signaling throughout Drosophila development. Despite a recent study describing the restriction of DPP signaling via putative ubiquitin E3 ligase dSmurf (1), the molecular mechanisms of how dSmurf affects DPP signaling remain unexplored. Toward this goal we demonstrated the degradation of phosphorylated MAD by dSmurf. dSmurf selectively interacted with MAD, but not Medea and Dad, and the MAD-dSmurf interaction was induced by constitutively active DPP type I receptor thickveins. Wild type dSmurf, but not its C1029A mutant, mediated ubiquitination-dependent degradation of MAD. Silencing of dSmurf using RNA interference stabilized MAD protein in Drosophila S2 cells. Targeted expression of dSmurf in various tissues abolished phosphorylated MAD and disrupted patterning and growth. In contrast, similar overexpression of inactive dSmurf(C1029A) showed no significant effects on development. We conclude that dSmurf specifically targets phosphorylated MAD to proteasome-dependent degradation and regulates DPP signaling during development.
Liang
Yao-Yun
YY
Michael E. DeBakey Department of Surgery, Department of Molecular & Cellular Biology, Ophthalmology, Program of Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Lin
Xia
X
Liang
Min
M
Brunicardi
F Charles
FC
ten Dijke
Peter
P
Chen
Zhihong
Z
Choi
Kwang-Wook
KW
Feng
Xin-Hua
XH
D000818:Animals; D019521:Body Patterning; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D016296:Mutagenesis; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014921:Wings, Animal / Q000254:growth & development
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D009097:Multienzyme Complexes; D014157:Transcription Factors; D025801:Ubiquitin; C064196:dpp protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases