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On page 707, Topper et al. report that an excess of Cdc34, a ubiquitin ligase, prevents the association of CENP-E with kinetochores. A reduction in the levels of kinetochore-localized CENP-E occurs normally during the progression from prometaphase to metaphase (Hoffman, D.B., et al. 2001. Mol. Biol. Cell. 12:1995–2009), as kinetochores reduce in size while switching from microtubule-capture to microtubule-maintenance mode. Overexpression of Cdc34 may be accelerating and exaggerating this reduction process to the extent that kinetochores cannot set up proper connections to the spindle. The result is a failure to get beyond prometaphase.2 q) U( j' _6 N
9 B6 ~/ {6 n0 E! D; U* ^' [9 C( j
Progression from prometaphase to metaphase is also inhibited by the recently discovered protein Emi1. One simple model〞that excess Cdc34 triggers premature destruction of Emi1and thus premature loss of CENP-E〞does not appear to be tenable. Although a ubiquitin ligase is exerting the (possibly indirect) effect on CENP-E, Topper et al. show that ubiquitin-mediated proteolysis is not required. In their hands, excess Cdc34 plus a proteasome inhibitor still results in CENP-E loss and prometaphase arrest. This is yet another case where ubiquitin conjugation is acting as a regulator of protein function rather than as a marker for degradation." J1 T6 \ ]1 W5 z9 k |
$ j+ l# _5 M4 l3 [Any link from the overexpression result to a physiologically relevant process remains speculative. But with new antibodies to Cdc34, Topper et al. hope to address the true function of Cdc34 in mitosis.(CENP-E (red) no longer localizes to kint) |
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发表于 2009-3-5 23:40
发表于 2015-5-22 11:36
