What question did this study set out to answer?

To investigate whether AKT/PKB directly phosphorylates p21(Cip1/WAF1) and how this modification influences p21 stability, cell cycle complexes, and tumor cell survival.

March 1, 2002Journal of Biological ChemistryOpen Access

AKT/PKB Phosphorylation of p21Cip/WAF1 Enhances Protein Stability of p21Cip/WAF1 and Promotes Cell Survival

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Authors

YLYing LiSouth China Agricultural University DDDonald DowbenkoIndiana University Health LLLaurence A. LaskyTexas Biomedical Research Institute

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Implication

Laboratory study reveals that AKT/PKB phosphorylates and stabilizes p21 in cancer cells, indicating a direct mechanism driving tumor survival and chemoresistance.

Key Points

To investigate whether AKT/PKB directly phosphorylates p21(Cip1/WAF1) and how this modification influences p21 stability, cell cycle complexes, and tumor cell survival.
Examined in vitro and in vivo phosphorylation of p21 at Thr(145) and Ser(146) by the kinase AKT/PKB.
Evaluated PCNA binding affinity, cyclin D1-CDK4 complex assembly, and p21 turnover in glioblastoma cell lines with activated AKT/PKB.
Assayed cell survival and resistance against taxol-mediated cytotoxicity in glioblastoma models.
AKT/PKB directly phosphorylated p21 at Thr(145), disrupting PCNA binding, and at Ser(146), which markedly enhanced p21 protein stability.
Glioblastoma cell lines displaying hyperactivated AKT/PKB exhibited increased p21 protein half-life and greater resistance to taxol toxicity.
AKT/PKB directed the assembly and activation of cyclin D1-CDK4 complexes via coordinated modulation of p21 and cyclin D1 levels.

Cite This Study

Li et al. (2002) studied this question.

synapsesocial.com/papers/6a73ea9e2212a44d888ded0f https://doi.org/10.1074/jbc.m109062200

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Implication

Laboratory study reveals that AKT/PKB phosphorylates and stabilizes p21 in cancer cells, indicating a direct mechanism driving tumor survival and chemoresistance.

AKT/PKB Phosphorylation of p21Cip/WAF1 Enhances Protein Stability of p21Cip/WAF1 and Promotes Cell Survival

Discussion

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Implication

Key Points

Cite This Study

AKT/PKB Phosphorylation of p21Cip/WAF1 Enhances Protein Stability of p21Cip/WAF1 and Promotes Cell Survival

Discussion

Member takes

Implication

Key Points

Cite This Study

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