The presence of the Rb c-box peptide in the cytoplasm inhibits p210(bcr-abl) transforming function

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 p210(bcr-abl) positive myeloid cells, we i ntroduced a truncated form of the 3' end of the Rb cDNA encoding its last 1 73 amino acid residues (Rb C-box) which localize into the cytoplasm where t he p210(bcr-abl) transforming protein is found, into myeloid cells (32D) wh ich depends on the p210(bcr-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 act ivity of the p210(bcr-abl) oncoprotein and to suppress the IL3-independent growth phenotype of the 32D-p210 cells, The Rb C-box polypeptides did not s uppress the growth of the untransfected 32D parental cell line in methylcel lulose in the presence of IL3-conditioned medium, These results suggest tha t the cytoplasmic localization of the p210(bcr-abl) allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p 145(c-abl) kinase.