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Highly potent p21^WAF1^‐derived peptide inhibitors of CDK‐mediated pRb phosphorylation: Delineation and structural insight into their interactions with cyclin A by D.I. Zheleva; C. McInnes; A.-L. Gavine; N.Z. Zhelev; P.M. Fischer; D.P. Lane is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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**Abstract:** The tumour suppressor protein p21^WAF1^ plays a central role in regulating eukaryotic cell‐cycle progression. Through its association with G1‐ and S‐phase CDK complexes it regulates activation of the retinoblastoma protein (pRb) and E2F transcription factors. Recognition of CDK/cyclin complexes by p21 occurs, at least in part, through a protein–protein interaction with a binding groove on the cyclin subunit. The same groove has been shown to be involved in the recruitment of macromolecular CDK substrates, including pRb and E2F. Blocking of this recruitment site therefore prevents recognition and subsequent phosphorylation of CDK substrates and offers a therapeutic approach towards restoration of p21‐like tumour suppression. Starting from the C‐terminal cyclin‐binding domain of p21 we have identified the minimal and optimized bioactive ^152^HAKRRLIF^159^ peptide sequence with respect to CDK protein kinase inhibition where pRb is the substrate. The phosphorylation of histone H1, however, which does not contain a recognizable cyclin‐binding motif, was unaffected. Detailed structure−activity relationship investigations revealed that the determinants within this sequence a

Who reads Highly potent p21^WAF1^‐derived peptide inhibitors of CDK‐mediated pRb phosphorylation: Delineation and structural insight into their interactions with cyclin A?

Author

D.I. Zheleva; C. McInnes; A.-L. Gavine; N.Z. Zhelev; P.M. Fischer; D.P. Lane

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 1397-002X)

Published

2002

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)