¹Division of Hematology/Oncology, Department of Medicine, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA, USA

Correspondence: Dr JYJ Wang, Moores Cancer Center, Room 4328, School of Medicine, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0820, USA. E-mail: jywang@ucsd.edu

²Current address: Instituto de Ciências Biomédicas, Departamento de Anatomia, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro, 21.941-590, Brazil.

Received 16 August 2006; Revised 13 October 2006; Accepted 17 October 2006; Published online 18 December 2006.

Abstract

The retinoblastoma protein RB regulates cell proliferation, differentiation and apoptosis. Homozygous knockout of Rb in mice causes embryonic lethality owing to placental defects that result in excessive apoptosis. RB binds to a number of cellular proteins including the nuclear Abl protein and inhibits its tyrosine kinase activity. Ex vivo experiments have shown that genotoxic or inflammatory stress can activate Abl kinase to stimulate apoptosis. Employing the Rb-null embryos as an in vivo model of apoptosis, we have shown that the genetic ablation of Abl can reduce apoptosis in the developing central nervous system and the embryonic liver. These results are consistent with the inhibitory interaction between RB and Abl, and provide in vivo evidence for the proapoptotic function of Abl.