Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide from p16CDKN2/INK4A

@article{Fhraeus1996InhibitionOP,
  title={Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide from p16CDKN2/INK4A},
  author={Robin F{\aa}hraeus and Jes{\'u}s M Paramio and Kathryn L Ball and Sonia La{\'i}n and David Philip Lane},
  journal={Current Biology},
  year={1996},
  volume={6},
  pages={84-91}
}
Abstract Background: The CDKN2/INK4A tumour suppressor gene is deleted or mutated in a large number of human cancers. Overexpression of its product, p16, has been shown to block the transition through the G 1 /S phase of the cell cycle in a pRb-dependent fashion by inhibiting the cyclin D-dependent kinases cdk4 and cdk6. Reconstitution of p16 function in transformed cells is therefore an attractive target for anti-cancer drug design. Results We have identified a 20-residue synthetic peptide… Expand
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The cell cycle in mammalian cells is regulated by a series of cyclins and cyclin-dependent kinases (CDKs). The G1/S checkpoint is mainly dictated by the kinase activities of the cyclin D-CDK4 and/orExpand
Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16
TLDR
It is shown that wild-type pi6 arrests normal diploid cells in late Gl, whereas a tumour-associated mutant of pi6 does not, and the ability ofpi6 to induce cell-cycle arrest is lost in cells lacking functional RB, including primary fibroblasts from Rb-/- mouse embryos. Expand
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P16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein, and inhibits the catalytic activity of theCDK4/cyclin D enzymes. Expand
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PCNA and the cell-cycle regulator p21WAF1 interact in vivo, and it is shown that this interaction requires the central loop of PCNA and an eight amino-acid motif from the carboxyl terminus of p21 WAF1. Expand
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TLDR
An 18-kD human protein, p18, is identified that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B) and exhibits no detectable interaction with the other known CDKs. Expand
Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6
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It is reported here that pi6 can act as a potent and specific inhibitor of progression through the Gl phase of the cell cycle, and it is demonstrated that several tumour-derived alleles of p16 encode functionally compromised proteins. Expand
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TLDR
A new member of the p16INK4 family is isolated, p15INK4B, which is induced ∼30-fold in human keratinocytes by treatment with TGF-β, suggesting that pi5 may act as an effector of T GF-β-mediated cell cycle arrest. Expand
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