pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels.
A key difference among the three structurally similar pRB family members is that only pRB is a tumor suppressor. Identification of distinctive functional differences between pRB and p107/p130 therefore holds promise for a better understanding of the tumor suppression mechanisms of pRB. Enigmatically, pRB and p107 have been shown to have indistinguishable growth suppression activities when studied in the pRB-deficient Saos-2 cell system. In this study, we discovered that, when expressed at physiologically relevant levels, pRB and p107 had distinctive effects in causing growth suppression. pRB induced cellular p130 levels while p107 repressed them. p107, but not pRB, blocked cells inside S phase in addition to G1 arrest. In contrast, no qualitative differences were identified in their abilities to repress the expression of a set of suspected pRB/E2F repression target genes. These results indicate that pRB and p107 possess different growth suppression effects, despite the fact that they have similar E2F repression effects.
Jiang
H
H
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Karnezis
A N
AN
Tao
M
M
Guida
P M
PM
Zhu
L
L
D001859:Bone Neoplasms / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases