Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 376, Issue 3, Pages 827-838Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2007.12.016
Keywords
cell cycle; cyclin-dependent kinase inhibitor; disordered protein; intrinsically unstructured protein; p27(Kip1)
Categories
Funding
- NCI NIH HHS [R01 CA082491, R01 CA082491-02, R01 CA082491-05, 2R01CA082491, 5P30CA021765, R01 CA082491-01A2, R01 CA082491-04, R01 CA082491-06A2, R01 CA082491-03, P30 CA021765] Funding Source: Medline
Ask authors/readers for more resources
p27(Kip1) (p27), which controls eukaryotic cell division through interactions with cyclin-dependent kinases (Cdks), integrates and transduces promitogenic signals from various nonreceptor tyrosine kinases by orchestrating its own phosphorylation, ubiquitination and degradation. Intrinsic flexibility allows p27 to act as a conduit for sequential signaling mediated by tyrosine and threonine phosphorylation and ubiquitination. While the structural features of the Cdk/cyclin-binding domain of p27 are understood, how the C-terminal regulatory domain coordinates multistep signaling leading to p27 degradation is poorly understood. We show that the 100-residue p27 C-terminal domain is extended and flexible when p27 is bound to Cdk2/cyclin A. We propose that the intrinsic flexibility of p27 provides a molecular basis for the sequential signal transduction conduit that regulates p27 degradation and cell division. Other intrinsically unstructured proteins possessing multiple sites of posttranslational modification may participate in similar signaling conduits. (C) 2007 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available