E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development

• DOI: 10.1371/journal.pgen.1000131
• Publication Date: 2008-07-17T22:36:02Z
• Authors: Madhura Kulkarni; Harold E. Smith
• Keywords: Ubiquitin-Protein Ligases; Genetic screen; F-box protein; Deubiquitinating enzyme; Model Organism

Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism dynamic control protein levels. The E1 ubiquitin-activating enzyme lies at apex ubiquitination cascade, its activity is necessary all subsequent steps in reaction. We have isolated a temperature-sensitive mutation Caenorhabditis elegans uba-1 gene, which encodes sole this organism. Manipulation UBA-1 different developmental stages reveals variety functions ubiquitination, including novel roles sperm fertility, body size, sex-specific development. Levels ubiquitin conjugates are substantially reduced mutant, consistent with activity. causes delays meiotic progression early embryo, process that known to be regulated by ubiquitin-mediated proteolysis. also demonstrates synthetic lethal interactions alleles anaphase-promoting complex, E3 ligase. sensitized genetic background identifying new vivo downstream components it one first conditional mutations reported metazoan animal model.