Abstract
In order to test if the carboxyl terminal polypeptide of the Retinoblastoma (Rb) tumor suppressor protein, could be used to suppress the growth factor-independent growth phenotype of p210bcr-abl positive myeloid cells, we introduced a truncated form of the 3′ end of the Rb cDNA encoding its last 173 amino acid residues (Rb C-box) which localize into the cytoplasm where the p210bcr-abl transforming protein is found, into myeloid cells (32D) which depends on the p210bcr-abl protein for IL3 growth factor-independent growth (32D-p210). The expression of the plasmid vectors carrying the Rb C-box cDNAs was shown to inhibit the abl tyrosine specific protein kinase activity of the p210bcr-abl oncoprotein and to suppress the IL3-independent growth phenotype of the 32D-p210 cells. The Rb C-box polypeptides did not suppress the growth of the untransfected 32D parental cell line in methylcellulose in the presence of IL3-conditioned medium. These results suggest that the cytoplasmic localization of the p210bcr-abl allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p145c-abl kinase.
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Acknowledgements
We thank Dr David Baltimore for providing the plasmid pGD-p210 (Daley et al., 1993) and Dr Hermann Bujard (Gossen and Bujard, 1992) for providing the plasmids pUHD15-1neo, pUHC13-3 and pUHD10-3. The authors are grateful for the support of NCI grants (PO1 CA55164 and PO1 CA49639), the Bush Leukemia Research Fund, the Anderson Chair for Cancer Research to ABD in the U.T.M.D. Anderson Cancer Center, and the Ensign Professorship of Medicine to ABD at the Yale University School of Medicine, and the Hull Development Fund at the Yale Cancer Center.
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Guo, XY., Balague, C., Wang, T. et al. The presence of the Rb c-box peptide in the cytoplasm inhibits p210bcr-abl transforming function. Oncogene 18, 1589–1595 (1999). https://doi.org/10.1038/sj.onc.1202479
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DOI: https://doi.org/10.1038/sj.onc.1202479