Role of the retinoblastoma protein in cell cycle arrest mediated by a novel cell surface proliferation inhibitor.
A novel cell regulatory sialoglycopeptide (CeReS-18), purified from the cell surface of bovine cerebral cortex cells has been shown to be a potent and reversible inhibitor of proliferation of a wide array of fibroblasts as well as epithelial-like cells and nontransformed and transformed cells. To investigate the possible mechanisms by which CeReS-18 exerts its inhibitory action, the effect of the inhibitor on the posttranslational regulation of the retinoblastoma susceptibility gene product (RB), a tumor suppressor gene, has been examined. It is shown that CeReS-18 mediated cell cycle arrest of both human diploid fibroblasts (HSBP) and mouse fibroblasts (Swiss 3T3) results in the maintenance of the RB protein in the hypophosphorylated state, consistent with a late G1 arrest site. Although their normal nontransformed counterparts are sensitive to cell cycle arrest mediated by CeReS-18, cell lines lacking a functional RB protein, through either genetic mutation or DNA tumor virus oncoprotein interaction, are less sensitive. The refractory nature of these cells is shown to be independent of specific surface receptors for the inhibitor, and another tumor suppressor gene (p53) does not appear to be involved in the CeReS-18 inhibition of cell proliferation. The requirement for a functional RB protein product, in order for CeReS-18 to mediate cell cycle arrest, is discussed in light of regulatory events associated with density-dependent growth inhibition.
Enebo
D J
DJ
Center for Basic Cancer Research, Kansas State University, Manhattan 66506-4903.
Fattaey
H K
HK
Moos
P J
PJ
Johnson
T C
TC
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000502:physiology*; D012795:Sialoglycoproteins / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016160:Retinoblastoma Protein; D012795:Sialoglycoproteins