Regulation of CHK1 Stability by the Ubiquitin Proteasome System
Date of Award
Doctor of Philosophy (PhD)
In response to replication or genotoxic stress, cells activate DNA damage checkpoints to maintain genome stability. The CHK1 protein kinase is essential for the S- and G2-phase DNA damage checkpoints. During checkpoint signaling, CHK1 undergoes post-translational modifications that modulate its activation and its destruction. ATR-mediated phosphorylation of CHK1 is required for CHK1 activation and checkpoint signaling while ubiquitination of CHK1 causes its destruction, which contributes to checkpoint termination. CHK1 ubiquitination is controlled by two distinct E3 ubiquitin ligases including CUL1-based E3 ligase (CRL1) and CUL4A-based E3 ligase (CRL4). My thesis studies identified two proteins that target CHK1 to CRL4 and I discovered a mechanism to explain how two distinct E3 ubiquitin ligases cooperate to regulate CHK1 abundance in vivo.
Chair and Committee
Helen M Piwnica-Worms
David C Beebe, Peter M J Burgers, Gregory D Longmore, Sheila A Stewart, Jason D Weber
Huh, Jiwon, "Regulation of CHK1 Stability by the Ubiquitin Proteasome System" (2012). Arts & Sciences Electronic Theses and Dissertations. 32.
Permanent URL: https://doi.org/10.7936/K7MK69TF