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- W2034707594 abstract "We have previously demonstrated that the apoptotic signaling pathway in K(+)-deprived cerebellar granule neurons involves a caspase-dependent cleavage of the retinoblastoma protein (Rb). Here, we have further investigated the functional consequences of this cleavage on two Rb-binding partners: the oncoprotein Mdm2 and the transcription factor E2F-1. A K(+) deprivation time course leads to a caspase inhibitor-sensitive degradation of Mdm2. Experimental blockade of Mdm2 expression with antisense oligodeoxynucleotides (ODN) results in neuronal death, suggesting an active role of Mdm2 in neuroprotection. By contrast, the E2F-1 protein accumulates in a caspase-independent manner following K(+) withdrawal, a consequence of increased gene transcription. This is likely to result from the rapid cyclin-dependent kinase 4 activation observed in LK, that correlates with a transient Rb phosphorylation. Counteracting E2F-1 upregulation with antisense ODNs prevents neuronal loss. Taken together, these data demonstrate that Rb is a central player in regulating both caspase-dependent and -independent events leading to apoptosis." @default.
- W2034707594 created "2016-06-24" @default.
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- W2034707594 date "2001-02-01" @default.
- W2034707594 modified "2023-09-25" @default.
- W2034707594 title "Regulation of the Retinoblastoma-Dependent Mdm2 and E2F-1 Signaling Pathways during Neuronal Apoptosis" @default.
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- W2034707594 doi "https://doi.org/10.1006/mcne.2000.0928" @default.
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