Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system.

摘要: Abstract Extensive apoptosis occurs in the nervous system of mouse embryos homozygous mutant for a targeted disruption retinoblastoma (Rb) gene. This cell death is present both central (CNS) and peripheral systems (PNS) associated with abnormal S phase entry normally post-mitotic neurons. Aberrant proliferation CNS correlates increased free E2F DNA binding activity expression cyclin E, an target gene critical cycle regulator. Cell accompanied by levels p53 tumor suppressor product gene, p21Waf-1/Cip-1. However, induction not observed PNS Rb-mutant embryos, nor does loss function inhibit PNS. Surprisingly, p21Waf-1/Cip-1 induced sensory ganglia p53-independent manner. Although prevents it restore normal proliferative control.