2022年9月7日 · Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell...

CDK4蛋白的T-loop区具有一小段卷曲螺旋结构(氨基酸残基序列162-171)。 这一结构会阻止底物进入活性位点。 利用CDK4与CDK6蛋白晶体结构，可以构建一个CDK4蛋白的“杂合状态”，进而用于抑制剂的设计。

Of the four INK4 proteins, p16 INK4A seems to play a critical role in senescence and tumor suppression in human cells [reviewed in 10, 13]. p16 is exclusively composed of four ankyrin repeat motifs, which are relatively well conserved motifs of 31-34 amino acids that mediate protein-protein interactions.

Deregulation of the p16(INK4a)-Cdk4/6-Rb pathway is commonly detected in patients with glioblastoma multiforme (GBM) and is a rational therapeutic target. Here, we characterized the p16(INK4a)-Cdk4/6-Rb pathway in the Mayo panel of GBM xenografts, established from primary tissue samples from patient …

【摘要】 抑癌基因p16ink4a在特异地抑制 CDK4及CDK6在控制细胞生长、 抑制肿瘤发生、 促进细胞衰老等方面发挥关键生物学作用, 该基因失活后造成了细胞周期调控失常,使得细胞异常增殖,造成了肿瘤发生、 发展, 本文就近几年来相关它在染色体上定位、 结构以及在 ...

2021年11月1日 · We demonstrate that Pos3AaTM-mCherry-p16 fusion crystals can efficiently deliver p16 protein, a CDK4/6 inhibitor frequently inactivated in human cancers, into p16-deficient UM-SCC-22A cells, where it promotes significant G1 cell cycle arrest and cell growth inhibition.

Whereas P16 is able to bind to and suppress the transactivational activity of NF-κB, IκBα, a specific inhibitor of NF-κB, competes with P16 for CDK4 binding and inhibits CDK4-mediated phosphorylation of pRb as potently as P16 does .

Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 ...

2025年1月17日 · CDK activity is controlled through phosphorylation and inhibition by CDK inhibitors, such as p16. Mutations in p16 can lead to diseases such as cancer. This study examines a series of p16 mutants and their molecular interactions with CDK4 using modelling, molecular dynamics simulations, and docking studies.

The p16(INK4a) tumor suppressor, whose expression is inhibited in a high number of cancers, binds to Cdk4/6 and inhibits phosphorylation of the retinoblastoma protein, forcing cells to remain in the G1 phase and therefore, arresting cell division.