Kumar P and Wang CC (2005) Depletion of anaphase-promoting complex or cyclosome (APC/C) subunit homolog APC1 or CDC27 of Trypanosoma brucei arrests the procyclic form in metaphase but the bloodstream form in anaphase. J Biol Chem 280(36):31783-91
Abstract: The anaphase-promoting complex or cyclosome (APC/C) is a multi-protein subunit E3 ubiquitin ligase complex that controls segregation of chromosomes and exit from mitosis in eukaryotes. It triggers elimination of key cell cycle regulators such as securin and mitotic cyclins during mitosis by polyubiquitinating them for proteasome degradation. Seven core subunit homologs of APC/C (Apc1, Apc2, Apc11, Cdc16, Cdc23, Cdc27 and Doc1) were identified in Trypanosoma brucei genome database. Expression of six of them was individually ablated by RNA interference (RNAi) in both the procyclic and bloodstream forms of T. brucei. Only the Cdc27 and Apc1 depleted cells were enriched in the G2/M phase with inhibited growth. Further studies indicated that T. brucei Apc1 and Cdc27 failed to complement the corresponding deletion mutants of budding yeast. But their depletion from procyclic-form T. brucei enriched cells with two kinetoplasts and an enlarged nucleus possessing short metaphase like mitotic spindles, suggesting that Apc1 and Cdc27 may play essential roles in promoting anaphase in the procyclic form. Their depletion from the bloodstream form, however, enriched cells with two kinetoplasts and two nuclei connected through a microtubule bundle suggesting a late anaphase arrest. This is the first time functional APC/C subunit homologs were identified in T. brucei. The apparent differential activities of this putative APC/C in two distinct developmental stages suggest an unusual function. The apparent lack of functional involvement of some of the other individual structural subunit homologs of APC/C may indicate the structural uniqueness of T. brucei APC/C.
|Status: Published||Type: Journal Article||PubMed ID: 15994309|
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