2007
DOI: 10.1523/jneurosci.5110-06.2007
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Phosphatidylinositol 3-Akt-Kinase-Dependent Phosphorylation of p21Waf1/Cip1as a Novel Mechanism of Neuroprotection by Glucocorticoids

Abstract: The role of glucocorticoids in the regulation of apoptosis remains incongruous. Here, we demonstrate that corticosterone protects neurons from apoptosis by a mechanism involving the cyclin-dependent kinase inhibitor p21 Waf1/Cip1 deficiency abrogate the neuroprotection by corticosterone, whereas overexpression of p21 Waf1/Cip1 suffices to protect neurons from apoptosis. We identify p21Waf1/Cip1 as a novel antiapoptotic factor for postmitotic neurons and implicate p21 Waf1/Cip1 as the molecular target of neurop… Show more

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Cited by 61 publications
(67 citation statements)
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“…The cytoplasmic localization of p21 can be caused by phosphorylation of Thr145 located in the NLS of p21 (11,27). Upon phosphorylation of the NLS domain by p-Akt, phosphorylated p21 (p-p21) becomes more stable and dynamically shuttles between the nucleus and the cytoplasm (11,27,28). In untreated and cisplatin-treated EC cells, p-p21 was detectable with WB (Supplemental Figure 4A).…”
Section: Figurementioning
confidence: 99%
“…The cytoplasmic localization of p21 can be caused by phosphorylation of Thr145 located in the NLS of p21 (11,27). Upon phosphorylation of the NLS domain by p-Akt, phosphorylated p21 (p-p21) becomes more stable and dynamically shuttles between the nucleus and the cytoplasm (11,27,28). In untreated and cisplatin-treated EC cells, p-p21 was detectable with WB (Supplemental Figure 4A).…”
Section: Figurementioning
confidence: 99%
“…The release of lactate dehydrogenase (LDH) was determined as a marker for cell membrane disintegrity in the supernatant medium. Propidium iodide (PI) was added to naive cultures and pictures were taken as described recently (Harms et al, 2007). Cell counts of at least 2000 neurons per condition were performed in at least triplicate experiments.…”
Section: Oxygen-glucose Deprivation Of Primary Mouse Cortical Neuronamentioning
confidence: 99%
“…Apart from its function in the cell cycle, there is evidence that p21 is a direct inhibitor of apoptosis (Suzuki et al, 1998). Moreover, Harms et al (2007) show that activation of p21 via phosphorylation and translocation into the cytoplasm in neurons prevents apoptosis. Hence, an upregulation of nuclear p21 by MIF can be envisaged to increase neuronal cell death upon ischemia.…”
Section: Cell Death Promoting Action Of Macrophage Migration Inhibitomentioning
confidence: 99%