Document Type
Article
Publication Date
2009
Publication Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume
284
Issue
5
First Page
2617
Last Page
2627
Abstract
Spy1A is a cyclin-like protein required for progression through the G(1)/S phase of the cell cycle. Elevated Spy1A protein levels have been implicated in tumorigenesis and are attributed to overriding the DNA damage response and enhancing cell proliferation. Understanding how Spy1A is produced and degraded is essential in resolving how it contributes to normal and abnormal growth processes. Herein, we demonstrate that Spy1A is degraded in a cell cycle-dependent manner during mitosis via the ubiquitin-proteasome system. We have resolved the E3 ligase and essential phosphorylation sites mediating Spy1A degradation. Furthermore, we have determined that non-degradable forms of Spy1A do not trigger cell cycle arrest but, rather, contribute to uncontrolled cell growth. Further investigation into the regulation of Spy1A may reveal novel strategies for understanding the etiology and progression of specific growth disorders.
DOI
10.1074/jbc.M804847200
Recommended Citation
Al Sorkhy, Mohammad; Craig, Ryan; Market, Brenna; Ard, Ryan; and Porter, Lisa A., "The Cyclin-dependent Kinase Activator, Spy1A, Is Targeted for Degradation by the Ubiquitin Ligase NEDD4" (2009). JOURNAL OF BIOLOGICAL CHEMISTRY, 284, 5, 2617-2627.
https://scholar.uwindsor.ca/biologypub/36