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Reduction of apoptosis in Rb-deficient embryos via Abl knockout

Oncogene volume 26, pages 3868–3877 (2007)Cite this article

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.

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Acknowledgements

We thank Rimma Levenzon for technical support. HLB is supported by CNPq (Brazil). This study was funded by a grant from the National Institutes of Health, USA to JYJW (CA58320).

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  1. H L Borges

    Present 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

Authors and Affiliations

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

    H L Borges, I C Hunton & J Y J Wang

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Correspondence to J Y J Wang.

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Borges, H., Hunton, I. & Wang, J. Reduction of apoptosis in Rb-deficient embryos via Abl knockout. Oncogene 26, 3868–3877 (2007). https://doi.org/10.1038/sj.onc.1210157

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