예쁜꼬마선충에서의 수모화(Sumoylation)에 관한연구

Abstract

Sumoylation is a post-translation modification that attaches an SUMO (small ubiquitin-like protein modifier) protein attached to a lysine residue on its target protein. Sumoylation, like ubiquitination, involves a SUMO activating enzyme (E1), a SUMO conjugating enzyme (E2), and SUMO ligases (E3). Yet, sumoylation is distinct from ubiquitination in that it serves diverse functions including protein interaction, activity, localization, and stability rather than a single role in targeted protein degradation. Known target substrates of sumoylation are mainly transcription factors and chromatin remodeling related proteins. Therefore, sumoylation regulates several important biological processes. Recently, the C. elegans SUMO protein SMO-1 was characterized and showed biological roles in gonadal and uterine-vulval morphogenesis. I show here that the C. elegans SUMO-conjugating enzyme UBC-9 plays a similar role in vulval morphogenesis. UBC-9 is the only known small ubiquitin-like protein modifier (SUMO)-conjugating enzyme in the C. elegans genome. C. elegans amino acid sequence of ubc-9 is 76% identical and 91% similar to human. I characterized a C. elegans ubc-9 null mutant. Interestingly, this mutant show protruding vulva (Pvl) and sterile (Ste) phenotypes. Calreticulin and calnexin are endoplasmic reticulum Ca2+ binding chaperone protein, important for heat shock stress. Sumoylation processes are also known to be up-regulated in ionizing radiation and heat shock stress. Here I show that crt-1 is up-regulated by knockout of sumoylation genes. Therefore, I analyzed the putative binding transcription factors in calreticulin promoter region and confirmed the binding of these transcription factors at the RNAi screening method.