Today, it is widely accepted that proteins that lack highly defined globular three-dimensional structures, termed IDPs (intrinsically disordered proteins), play key roles in myriad biological processes. Our understanding of how intrinsic disorder mediates biological function is, however, incomplete. In the present paper, we review disorder-mediated cell cycle regulation by two intrinsically disordered proteins, p21 and p27. A structural adaptation mechanism involving a stretchable dynamic linker helix allows p21 to promiscuously recognize the various Cdk (cyclin-dependent kinase)–cyclin complexes that regulate cell division. Disorder within p27 mediates transmission of an N-terminal tyrosine phosphorylation signal to a C-terminal threonine phosphorylation, constituting a signalling conduit. These mechanisms are mediated by folding upon binding p21/p27′s regulatory targets. However, residual disorder within the bound state contributes critically to these functional mechanisms. Our studies provide insights into how intrinsic protein disorder mediates regulatory processes and opportunities for designing drugs that target cancer-associated IDPs.
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October 2012
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Conference Article|
September 19 2012
Cell cycle regulation by the intrinsically disordered proteins p21 and p27
Mi-Kyung Yoon;
Mi-Kyung Yoon
1St. Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, U.S.A.
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Diana M. Mitrea;
Diana M. Mitrea
1St. Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, U.S.A.
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Li Ou;
Li Ou
1St. Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, U.S.A.
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Richard W. Kriwacki
Richard W. Kriwacki
1
1St. Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, U.S.A.
1To whom correspondence should be addressed (emailRichard.Kriwacki@stjude.org).
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Publisher: Portland Press Ltd
Received:
April 11 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (5): 981–988.
Article history
Received:
April 11 2012
Citation
Mi-Kyung Yoon, Diana M. Mitrea, Li Ou, Richard W. Kriwacki; Cell cycle regulation by the intrinsically disordered proteins p21 and p27. Biochem Soc Trans 1 October 2012; 40 (5): 981–988. doi: https://doi.org/10.1042/BST20120092
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