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

  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},

Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1.

It is concluded that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:C DK2 complexes at the restriction point and is thus nonredundant with cyclin Cdk2 in late G1.

Induction of p21WAF1/CIP1and Inhibition of Cdk2 Mediated by the Tumor Suppressor p16INK4a

It is indicated that p21-mediated inhibition of cdk2 contributes to the cell cycle arrest imposed by p16 and is a potential point of cooperation between the p16/pRB and p14ARF/p53 tumor suppressor pathways.

Structure of the cyclin-dependent kinase inhibitor p19Ink4d

The structure of the p19Ink4d protein, determined by NMR spectroscopy, indicates that most mutations to the p16Ink 4a gene, which result in loss of function, are due to incorrectly folded and/or insoluble protein.

Structural Analysis of the Inhibition of Cdk4 and Cdk6 by p16INK4a through Molecular Dynamics Simulations

Results from molecular dynamics simulations provide a better understanding of the role of the T-loop conformation, a fragment of Cdks, and the way the ATP binding-site is distorted upon binding of p16INK4a.

Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a

Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.

Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product.

Fascaplysin will prove to be a useful tool in studying the consequence of Cdk4 inhibition, especially in cells containing inactivated p16, and caused G1 arrest and prevented pRb phosphorylation at sites implicated as being specific for Cdk 4 kinase.

Selective in vivo and in vitro effects of a small molecule inhibitor of cyclin-dependent kinase 4.

The specificity of CINK4 for Cdk4 raises the possibility that this small molecule or one with a similar structure could have therapeutic value and slows tumor growth in vivo.

Role of cell cycle control and cyclin-dependent kinases in breast cancer.

The regulation of cell cycle and proliferation has been extensively studied in the last few years and a consensus paradigm of cell cycle regulation has been developed [1,2]. According to this



Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4

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/or

A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

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.

Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6

Introduction of a vector encoding p19 into mouse NIH 3T3 cells leads to constitutive p19 synthesis, inhibits cyclin D1-CDK4 activity in vivo, and induces G1 phase arrest, consistent with the possibility that INK4 proteins limit the activities of CDKs once cells exit G 1 phase.

Inhibition of ras-induced proliferation and cellular transformation by p16INK4

Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle induced by oncogenic Ha-Ras, and this block was relieved by coexpression of a catalytically inactive CDK4 mutant, providing direct evidence that p16ink4 can inhibit cell growth.

Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition

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.

Lack of cyclin D‐Cdk complexes in Rb‐negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product.

It is suggested that in cells in which the function of Rb has been compromised, p16 competes with D cyclins for binding to Cdk4 and Cdk6 and prevents formation of active complexes, and DNA tumour virus oncoproteins do not disrupt cyclin D1‐Cdk4 complexes in cells lacking p16.

pl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest

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.

Mutations associated with familial melanoma impair p16INK4 function

Cell division is controlled by a series of positive and negative regulators which act at sequential points throughout the cell cycle. Disturbance of these checks could contribute to cancer by