tailieunhanh - báo cáo khoa hoc : Overexpression of Dsk2 ⁄dUbqln results in severe developmental defects and lethality in Drosophila melanogaster that can be rescued by overexpression of the p54 ⁄Rpn10 ⁄S5a proteasomal subunit

Polyubiquitin receptors execute the targeting of polyubiquitylated proteins to the 26S proteasome. In vitro studies indicate that disturbance of the physiological balance among different receptor proteins impairs the prote-asomal degradation of polyubiquitylated proteins. | IFEBS Journal Overexpression of Dsk2 dUbqln results in severe developmental defects and lethality in Drosophila melanogaster that can be rescued by overexpression of the p54 Rpn10 S5a proteasomal subunit Zoltán Lipinszki Margit Pal Olga Nagy Peter Deak Eva Hunyadi-Gulyas and Andor Udvardy Institute of Biochemistry BiologicalResearch Centre of the Hungarian Academy of Sciences Szeged Hungary Keywords 26S proteasome Dsk2 dUbqln p54 Rpn10 S5a polyubiquitin receptors ubiquitylation Correspondence A. Udvardy Institute of Biochemistry Biological Research Centre of the Hungarian Academy of Sciences PO Box 521. H-6701 Szeged Hungary Fax 36 62 433 506 Tel 36 62 599 664 E-mail udvardy@ Received 17 July 2011 revised 6 September 2011 accepted 26 September 2011 doi Polyubiquitin receptors execute the targeting of polyubiquitylated proteins to the 26S proteasome. In vitro studies indicate that disturbance of the physiological balance among different receptor proteins impairs the prote-asomal degradation of polyubiquitylated proteins. To study the physiological consequences of shifting the in vivo equilibrium between the p54 Rpn10 proteasomal and the Dsk2 dUbqln extraproteasomal polyubiquitin receptors transgenic Drosophila lines were constructed in which the overexpression or RNA interference-mediated silencing of these receptors can be induced. Flies overexpressing Flag-p54 were viable and fertile without any detectable morphological abnormalities although detectable accumulation of polyubiquitylated proteins demonstrated a certain level of proteolytic disturbance. Flag-p54 was assembled into the 26S proteasome and could fully complement the lethal phenotype of a p54 null mutant Drosophila line. The overexpression of Dsk2 caused severe morphological abnormalities in the late pupal stages leading to pharate adult lethality accompanied by a huge accumulation of highly polyubiquitylated proteins. The lethal phenotype of Dsk2 overexpression .