TY - JOUR
T1 - Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein
AU - Zhu, Liang
AU - Van Heuvel, Sander Den
AU - Helin, Kristian
AU - Fattaey, Ali
AU - Ewen, Mark
AU - Livingston, David
AU - Dyson, Nicholas
AU - Harlow, Ed
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - E1A
KW - E2F
KW - Growth suppression
KW - P107
KW - PRB
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M3 - Article
C2 - 8319904
AN - SCOPUS:0027313470
SN - 0890-9369
VL - 7
SP - 1111
EP - 1125
JO - Genes and Development
JF - Genes and Development
IS - 7
ER -