Date

August 2007

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Mind bomb I is a newly identified RING finger type E3 ubiquitin ligase with only a few known associated-proteins. Using a proteomic-based approach, I identified an array of associated-proteins of Mind bomb I, including the plus-ended kine sin Eg5. In this dissertation, I characterize in more detail the interaction between Mind bomb I and Eg5. Mind bomb 1 and Eg5 can co-immunoprecipitate, an association that requires the N terminal region of Mind bomb 1. Furthermore, Mind bomb 1 can promote the monoubiquitination of Eg5. Both Eg5 and Mind bomb 1 co-localize at the centrosome and alteration of their levels or activity cause centrosome defects. Specifically, Eg5 inhibition and Mind bomb overexpression can both cause excess centrosomes and centrioles. Conversely, Mind bomb 1-silencing can reduce the number of centrosomes produced in normal and Aphidicolin-induced centrosome duplication. Moreover, Eg5 overexpression can rescue Mindbomb1-induced centrosome overproduction. Together, these data indicate that Mind bomb I and Eg5 function in the same pathway to ensure the proper number of centrosomes. This novel finding of two critical regulators of the centrosome contributes to our understanding of how centrosome number is maintained.

Identifier

doi:10.6083/M4G15XVS

Division

Neuroscience Graduate Program

School

School of Medicine

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