title: Overexpression of ubiquitin carboxyl terminal hydrolase impairs multiple pathways during eye development in Drosophila melanogaster.
abstract: UCH-L1 (ubiquitin carboxyl terminal hydrolase L1) is well known as an enzyme that hydrolyzes polyubiquitin at its C-terminal to release ubiquitin monomers. Although the overexpression of UCH-L1 inhibits proteasome activity in cultured cells, its biological significance in living organisms has not been clarified in detail. Here, we utilized Drosophila as a model system to examine the effects of the overexpression of dUCH, a Drosophila homologue of UCH-L1, on development. Overexpression in the eye imaginal discs induced a rough eye phenotype in the adult, at least partly resulting from the induction of caspase-dependent apoptosis followed by compensatory proliferation. Genetic crosses with enhancer trap lines marking the photoreceptor cells also revealed that the overexpression of dUCH specifically impaired R7 photoreceptor cell differentiation with a reduction in activated extracellular-signal-regulated kinase signals. Furthermore, the dUCH-induced rough eye phenotype was rescued by co-expression of the sevenless gene or the Draf gene, a downstream component of the mitogen-activated protein kinase (MAPK) cascade. These results indicate that the overexpression of dUCH impairs R7 photoreceptor cell differentiation by down-regulating the MAPK pathway. Interestingly, this process appears to be independent of its pro-apoptotic function.
authors.affiliation: Department of Molecular and Environmental Biotechnology, University of Science, Vietnam National University in Ho Chi Minh City, Ho Chi Minh City, Vietnam. thaodp@hcmus.edu.vn
authors.forename: Dang Thi Phuong
authors.initials: DT
authors.lastname: Thao
authors.forename: Phan Nguyen Thuy
authors.initials: PN
authors.lastname: An
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Tran
authors.initials: T
authors.lastname: LinhThuoc
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure; D060227:Imaginal Discs / Q000166:cytology / Q000201:enzymology; D020935:MAP Kinase Signaling System; D008938:Mitosis; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000201:enzymology; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D043222:Ubiquitin Thiolesterase; D053148:Caspase 3