Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein.
The cellular protein p107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human p107 and have used this clone to study the function of p107. We show that, like pRB, p107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of p107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and p107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, p107 was able to block cell proliferation, whereas pRB could not, even though both proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and p107 was rescued differentially by various cell cycle regulators. Third, some mutants of p107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of p107 that is related, but not identical, to that of pRB.
Zhu
L
L
Massachusetts General Hospital Cancer Center, Charlestown 02129.
van den Heuvel
S
S
Helin
K
K
Fattaey
A
A
Ewen
M
M
Livingston
D
D
Dyson
N
N
Harlow
E
E
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D017502:Adenovirus E2 Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase; D006131:Growth Inhibitors; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000502:physiology; D050720:Retinoblastoma-Like Protein p107; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D017502:Adenovirus E2 Proteins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D009687:Nuclear Proteins; D011506:Proteins; C493844:RBL1 protein, human; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107