The retinoblastoma protein is essential for survival of postmitotic neurons.
The retinoblastoma protein (Rb) family members are essential regulators of cell cycle progression, principally through regulation of the E2f transcription factors. Growing evidence indicates that abnormal cell cycle signals can participate in neuronal death. In this regard, the role of Rb (p105) itself has been controversial. Germline Rb deletion leads to massive neuronal loss, but initial reports argue that death is non-cell autonomous. To more definitively resolve this question, we generated acute murine knock-out models of Rb in terminally differentiated neurons in vitro and in vivo. Surprisingly, we report that acute inactivation of Rb in postmitotic neurons results in ectopic cell cycle protein expression and neuronal loss without concurrent induction of classical E2f-mediated apoptotic genes, such as Apaf1 or Puma. These results suggest that terminally differentiated neurons require Rb for continuous cell cycle repression and survival.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Matthew G
MG
Andrusiak
Renaud
R
Vandenbosch
David S
DS
Park
Ruth S
RS
Slack
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000502:physiology*
D016160:Retinoblastoma Protein