p73 can suppress the proliferation of cells that express mutant p53

Amy C. Willis, Tara Pipes, Jianhui Zhu, Xinbin Chen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer, p73, a member of the p53 family, has been found to exhibit activity similar to that of p53, including the ability to induce growth arrest and apoptosis, p53 and p73 have a high percentage of similarity at several domains, including the DNA binding domain. This domain in p53 is the location of missense mutations in many human cancers. Mutant p53, which cannot suppress cell proliferation, has been found to have a dominant-negative activity that inactivates wild-type p53. To determine the effects of mutant p53 on wild-type p73, we have established cell lines expressing both mutant p53 and wild-type p73 in a dual-inducible system. This system expresses mutant p53 in a tetracycline-repressible system and p73β in an ecdysone-inducible system in a p53-null lung carcinoma parental cell line. We have found that wild-type p73β, in the presence of mutant p53, retains the ability to transactivate p21 and suppresses cell growth through induction of both cell cycle arrest and apoptosis. In addition, in cell lines expressing wild-type p53 and wild-type p73β, we have found that these proteins cooperate to additively transactivate p21 and suppress cell proliferation.

Original languageEnglish (US)
Pages (from-to)5481-5495
Number of pages15
JournalOncogene
Volume22
Issue number35
DOIs
StatePublished - Aug 21 2003
Externally publishedYes

Fingerprint

Aptitude
Cell Proliferation
Cell Line
Apoptosis
Ecdysone
Missense Mutation
Growth
Cell Cycle Checkpoints
Tetracycline
Tumor Suppressor Genes
Neoplasms
Carcinoma
Lung
Mutation
DNA
Proteins

Keywords

  • Apoptosis
  • Cell cycle arrest
  • p21
  • p53
  • p73

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

p73 can suppress the proliferation of cells that express mutant p53. / Willis, Amy C.; Pipes, Tara; Zhu, Jianhui; Chen, Xinbin.

In: Oncogene, Vol. 22, No. 35, 21.08.2003, p. 5481-5495.

Research output: Contribution to journalArticle

Willis, Amy C. ; Pipes, Tara ; Zhu, Jianhui ; Chen, Xinbin. / p73 can suppress the proliferation of cells that express mutant p53. In: Oncogene. 2003 ; Vol. 22, No. 35. pp. 5481-5495.
@article{45b336c122164055a57ce3bc32314753,
title = "p73 can suppress the proliferation of cells that express mutant p53",
abstract = "Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer, p73, a member of the p53 family, has been found to exhibit activity similar to that of p53, including the ability to induce growth arrest and apoptosis, p53 and p73 have a high percentage of similarity at several domains, including the DNA binding domain. This domain in p53 is the location of missense mutations in many human cancers. Mutant p53, which cannot suppress cell proliferation, has been found to have a dominant-negative activity that inactivates wild-type p53. To determine the effects of mutant p53 on wild-type p73, we have established cell lines expressing both mutant p53 and wild-type p73 in a dual-inducible system. This system expresses mutant p53 in a tetracycline-repressible system and p73β in an ecdysone-inducible system in a p53-null lung carcinoma parental cell line. We have found that wild-type p73β, in the presence of mutant p53, retains the ability to transactivate p21 and suppresses cell growth through induction of both cell cycle arrest and apoptosis. In addition, in cell lines expressing wild-type p53 and wild-type p73β, we have found that these proteins cooperate to additively transactivate p21 and suppress cell proliferation.",
keywords = "Apoptosis, Cell cycle arrest, p21, p53, p73",
author = "Willis, {Amy C.} and Tara Pipes and Jianhui Zhu and Xinbin Chen",
year = "2003",
month = "8",
day = "21",
doi = "10.1038/sj.onc.1206505",
language = "English (US)",
volume = "22",
pages = "5481--5495",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "35",

}

TY - JOUR

T1 - p73 can suppress the proliferation of cells that express mutant p53

AU - Willis, Amy C.

AU - Pipes, Tara

AU - Zhu, Jianhui

AU - Chen, Xinbin

PY - 2003/8/21

Y1 - 2003/8/21

N2 - Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer, p73, a member of the p53 family, has been found to exhibit activity similar to that of p53, including the ability to induce growth arrest and apoptosis, p53 and p73 have a high percentage of similarity at several domains, including the DNA binding domain. This domain in p53 is the location of missense mutations in many human cancers. Mutant p53, which cannot suppress cell proliferation, has been found to have a dominant-negative activity that inactivates wild-type p53. To determine the effects of mutant p53 on wild-type p73, we have established cell lines expressing both mutant p53 and wild-type p73 in a dual-inducible system. This system expresses mutant p53 in a tetracycline-repressible system and p73β in an ecdysone-inducible system in a p53-null lung carcinoma parental cell line. We have found that wild-type p73β, in the presence of mutant p53, retains the ability to transactivate p21 and suppresses cell growth through induction of both cell cycle arrest and apoptosis. In addition, in cell lines expressing wild-type p53 and wild-type p73β, we have found that these proteins cooperate to additively transactivate p21 and suppress cell proliferation.

AB - Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer, p73, a member of the p53 family, has been found to exhibit activity similar to that of p53, including the ability to induce growth arrest and apoptosis, p53 and p73 have a high percentage of similarity at several domains, including the DNA binding domain. This domain in p53 is the location of missense mutations in many human cancers. Mutant p53, which cannot suppress cell proliferation, has been found to have a dominant-negative activity that inactivates wild-type p53. To determine the effects of mutant p53 on wild-type p73, we have established cell lines expressing both mutant p53 and wild-type p73 in a dual-inducible system. This system expresses mutant p53 in a tetracycline-repressible system and p73β in an ecdysone-inducible system in a p53-null lung carcinoma parental cell line. We have found that wild-type p73β, in the presence of mutant p53, retains the ability to transactivate p21 and suppresses cell growth through induction of both cell cycle arrest and apoptosis. In addition, in cell lines expressing wild-type p53 and wild-type p73β, we have found that these proteins cooperate to additively transactivate p21 and suppress cell proliferation.

KW - Apoptosis

KW - Cell cycle arrest

KW - p21

KW - p53

KW - p73

UR - http://www.scopus.com/inward/record.url?scp=0041333921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041333921&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1206505

DO - 10.1038/sj.onc.1206505

M3 - Article

VL - 22

SP - 5481

EP - 5495

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 35

ER -