The presence of the Rb c-box peptide in the cytoplasm inhibits p210bcr-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 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 p210(bcr-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 p210(bcr-abl) allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p145(c-abl) kinase.
Guo
X Y
XY
Department of Internal Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Balague
C
C
Wang
T
T
Randhawa
G
G
Yuan
Z
Z
Bachier
C
C
Greenberger
J
J
Arlinghaus
R
R
Kufe
D
D
Deisseroth
A B
AB
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003114:Colony-Forming Units Assay; D018076:DNA, Complementary / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D016161:Genes, Retinoblastoma; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D010446:Peptide Fragments / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology*; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D018076:DNA, Complementary; D007377:Interleukin-3; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D016044:Fusion Proteins, bcr-abl; D013752:Tetracycline