Localization normally results from specific binding. Kimberly Collins, Suzanne Furuyama, and Sue Biggins (Fred Hutchinson Cancer Research Center, Seattle, WA) now report that localization can also be driven by degradation at every location but the target site.

The protein in question is Cse4. This budding yeast homologue of CENP-A is localized specifically to kinetochores, where it incorporates into nucleosomes. It may be one of the initial (although not necessarily sufficient) building blocks of a kinetochore.

Biggins noticed that Cse4 was marked for degradation by ubiquitin tags. A stable mutant of Cse4 was lethal and localized all over chromosome arms. By contrast, adding another degradation tag to Cse4 did not induce instability of the protein that had localized to the kinetochore.

The Seattle group plans to delete various kinetochore proteins to see if any one of them is responsible for protecting kinetochore-localized Cse4 from degradation. They will also use the more abundant nondegradable Cse4 mutant to continue searching for a loading factor—a factor that probably complements the degradation system to achieve Cse4 localization.

Reference:

Collins, K.A., et al.
2004
.
Curr. Biol.
14
:
1968
–1972.