Enhanced tumor cell growth suppression by an N-terminal truncated retinoblastoma protein.
The retinoblastoma (RB) gene encodes a nuclear phosphoprotein of 928 amino acids (pRB). Thus far, much effort in RB research has been focused on both the viral oncoprotein-binding domains and the C-terminal domain, whereas little is known about the N-terminal moiety of the protein. We report here that an N-terminal truncated RB protein of approximately 94 kDa (pRB94) exerts more potent cell growth suppression as compared to the full-length pRB protein in a diversity of tumor cell lines examined, including those having a normal endogenous RB gene. Tumor cells transfected with the pRB94-expressing plasmids displayed multiple morphological changes frequently associated with cellular senescence and/or apoptosis. They failed to enter S phase and rapidly died. The pRB94 expressed in recipient tumor cells had a longer half-life than the full-length pRB protein and tended to remain in an active un- or hypophosphorylated form. Since it has also been found that N-terminal truncated RB proteins often accumulated in growth-arrested and/or differentiated tumor cells, we suggest that N-terminal truncation of pRB may be one of the cellular mechanisms modulating the RB protein function in cell-cycle control.
Xu
H J
HJ
Center for Biotechnology, Baylor College of Medicine, Woodlands, TX 77381.
Xu
K
K
Zhou
Y
Y
Li
J
J
Benedict
W F
WF
Hu
S X
SX
D000818:Animals; D016367:Baculoviridae; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D016161:Genes, Retinoblastoma; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein