Involvement of Retinoblastoma Family Members and E2F/DP Complexes in the Death of Neurons Evoked by DNA Damage

• DOI: 10.1523/jneurosci.20-09-03104.2000
• Publication Date: 2018-04-05T02:15:51Z
• Authors: David S. Park; Erick J. Morris; Rod Bremner; Elizabeth Keramaris; Jaya Padmanabhan; Michele Rosenbaum; Michael L. Shelanski; Herbert M. Geller; Lloyd A. Greene
• Keywords: Retinoblastoma protein; E2F; Retinoblastoma

Neuronal death evoked by DNA damage requires cyclin-dependent kinase 4 (Cdk4) and 6 activity is accompanied elevation of cyclin D1-associated activity. Because Cdk4/6 phosphorylates retinoblastoma protein (pRb) family members that then modulate the transcriptional E2F/DP1 complexes, we examined involvement these components in damage-evoked neuronal death. Camptothecin induced rapid pRb p107 phosphorylation at a site followed selective loss Rb p107. The CDK inhibitor flavopiridol suppressed loss, implicating events. Moreover, appeared to be mediated caspases because it was blocked general caspase inhibitors. role pathway indicated observations virally expression mutated sites phosphorylation, including site, inhibited Finally, dominant-negative versions DP1, known compromise E2F activity, protects cortical neurons from camptothecin sympathetic UV treatment. Taken together, results implicate CDK–pRb/E2F/DP as required element damage.