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      Cell cycle regulation by the intrinsically disordered proteins, p21 and p27

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          Synopsis

          Today, it is widely accepted that proteins that lack highly defined, globular structures, 3D, termed “intrinsically disordered proteins (IDPs)”, play key roles in myriad biological processes. Our understanding of how intrinsic disorder mediates biological function is, however, incomplete. Here, 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 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 signaling 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 provide opportunities for designing drugs that target cancer-associated IDPs.

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          Author and article information

          Contributors
          Journal
          7506897
          3328
          Biochem Soc Trans
          Biochem. Soc. Trans.
          Biochemical Society transactions
          0300-5127
          1470-8752
          2 March 2020
          October 2012
          11 March 2020
          : 40
          : 5
          : 981-988
          Affiliations
          St. Jude Children’s Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, USA
          St. Jude Children’s Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, USA
          St. Jude Children’s Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, USA
          St. Jude Children’s Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis TN, 38105, USA
          Author notes
          [* ]corresponding author: Tel: 901-595-3290, Fax: 901-595-3032, Richard.Kriwacki@ 123456stjude.org
          Article
          PMC7065656 PMC7065656 7065656 nihpa1566422
          10.1042/BST20120092
          7065656
          22988851
          b35deee9-5bf2-4cc3-b79d-0b774cf05ede
          History
          Categories
          Article

          p27,tyrosine phosphorylation,Cell cycle regulator,intrinsically disordered proteins,p21

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