title: Drosophila Smt3 negatively regulates JNK signaling through sequestering Hipk in the nucleus.
abstract: Post-translational modification by the small ubiquitin-related modifier (SUMO) is important for a variety of cellular and developmental processes. However, the precise mechanism(s) that connects sumoylation to specific developmental signaling pathways remains relatively less clear. Here, we show that Smt3 knockdown in Drosophila wing discs causes phenotypes resembling JNK gain of function, including ectopic apoptosis and apoptosis-induced compensatory growth. Smt3 depletion leads to an increased expression of JNK target genes Mmp1 and puckered. We show that, although knockdown of the homeodomain-interacting protein kinase (Hipk) suppresses Smt3 depletion-induced activation of JNK, Hipk overexpression synergistically enhances this type of JNK activation. We further demonstrate that Hipk is sumolylated in vivo, and its nuclear localization is dependent on the sumoylation pathway. Our results thus establish a mechanistic connection between the sumoylation pathway and the JNK pathway through the action of Hipk. We propose that the sumoylation-controlled balance between cytoplasmic and nuclear Hipk plays a crucial role in regulating JNK signaling.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Guiping
authors.initials: G
authors.lastname: Du
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.forename: Xuehong
authors.initials: X
authors.lastname: Liang
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins; D058207:Sumoylation
chemical_list: D029721:Drosophila Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C490960:smt3 protein, Drosophila; D011494:Protein Kinases; C501861:HIPK protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases