@article{b5b02a8852ea4fe28efd16f73831a569,
title = "Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles",
abstract = "Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification. The converse occurred in cells lacking wild-type p53 expression. Expression of wild-type p53 in transformants of immortal and tumor cells containing mutant p53 alleles restored G1 control and reduced the frequency of gene amplification to undetectable levels. These studies reveal that p53 contributes to a metabolically regulated G1 checkpoint, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression.",
author = "Yuxin Yin and Tainsky, {Michael A.} and Bischoff, {Farideh Z.} and Strong, {Louise C.} and Wahl, {Geoffrey M.}",
note = "Funding Information: We thank Dr. George Stark for generously sending his human CAD gene cosmid prior to its publication, Dr. Jeffrey Davidson for providing us with several CAD gene genomic clones, Dr. Martin Haas for the p53 and Iux retroviruses, Dr. Bert Vogelstein for the pC55SCX3, and Dr. Ed Mercer for cell lines GM47.23 and pM47. We are especially grateful to Dr. Stephen O{\textquoteright}Gorman for his substantial editorial efforts and to Dr. Marguerite Vogt for her perceptive and critical comments throughout the course of this work. Drs. Alex Almasan, Walter Eckhart, Merl Hoek-stra, Tony Hunter, Mike McKeown, Bari Sefton, and Henry Sukov are acknowledged for helpful comments concerning the manuscript; Drs. Ruth Kelly, Jon Pines, and Yeong Wang for advice concerning the immunoprecipitation and cell cycle analyses; Joe Trotter for insightful suggestions and superb technical assistance with flow cytometry; Tian-Ai Wu and Olanike Akande for technical assistance: Peggy Sanders for help with manuscript preparation; and The Salk Photo Lab for preparation of the figures. Y. Y. is grateful for the support and encouragement of Dr. Xianmao Luo. This work was supported by NIH grant POlCA34936 to L. C. S. and M. A. T.; G. M. W. and Y. Y. were supported by NIH grant GM27754, and by a grant from the G. Harold and Leila Y. Mathers Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby",
year = "1992",
month = sep,
day = "18",
doi = "10.1016/0092-8674(92)90244-7",
language = "English (US)",
volume = "70",
pages = "937--948",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}