AI Article Synopsis
- A newly identified checkpoint pathway in early mitosis delays chromosome condensation when microtubule poisons are present, with chfr being the only implicated gene so far.
- Chfr has a RING domain and exhibits ubiquitin ligase activity, but its in vivo significance remains uncertain.
- Evidence suggests that Chfr functions in signaling mitotic stress through noncanonical Lys63-linked polyubiquitin chains, rather than targeting proteins for degradation by the proteasome.
Article Abstract
We recently described a novel checkpoint pathway that functions early in mitosis to delay chromosome condensation in response to microtubule poisons. The only gene implicated so far in this checkpoint pathway is chfr, whose protein product contains a RING domain and has ubiquitin ligase activity in vitro. The significance of this activity in vivo is unclear. A recent report suggested that the Chfr protein targets itself for proteasome-dependent degradation in mitotic cells through autoubiquitination. However, we observe that in mitosis Chfr exhibits a phosphorylation-dependent electrophoretic mobility shift with no change in overall protein levels. Further analysis of its ubiquitin ligase activity revealed that Chfr can catalyse the formation of noncanonical Lys63-linked polyubiquitin chains with Ubc13-Mms2 acting as the ubiquitin-conjugating enzyme. Ubc13-Mms2 and Lys63-polyubiquitin chains are not associated with targeting proteins to the proteasome, but rather with signaling cellular stress. We propose that Chfr may have a role in signaling the presence of mitotic stress induced by microtubule poisons.
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