p53 regulates a mitotic transcription program and determines ploidy in normal mouse liverCitation formats

  • External authors:
  • Sabrina A Stratton
  • Zeynep Coban
  • Jill M Schumacher
  • Markus Grompe
  • Andrew W Duncan
  • Michelle Craig Barton

Standard

p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. / Kurinna, Svitlana; Stratton, Sabrina A; Coban, Zeynep; Schumacher, Jill M; Grompe, Markus; Duncan, Andrew W; Barton, Michelle Craig.

In: Hepatology (Baltimore, Md.), Vol. 57, No. 5, 05.2013, p. 2004-2013.

Research output: Contribution to journalArticlepeer-review

Harvard

Kurinna, S, Stratton, SA, Coban, Z, Schumacher, JM, Grompe, M, Duncan, AW & Barton, MC 2013, 'p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver', Hepatology (Baltimore, Md.), vol. 57, no. 5, pp. 2004-2013. https://doi.org/10.1002/hep.26233

APA

Kurinna, S., Stratton, S. A., Coban, Z., Schumacher, J. M., Grompe, M., Duncan, A. W., & Barton, M. C. (2013). p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. Hepatology (Baltimore, Md.), 57(5), 2004-2013. https://doi.org/10.1002/hep.26233

Vancouver

Kurinna S, Stratton SA, Coban Z, Schumacher JM, Grompe M, Duncan AW et al. p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. Hepatology (Baltimore, Md.). 2013 May;57(5):2004-2013. https://doi.org/10.1002/hep.26233

Author

Kurinna, Svitlana ; Stratton, Sabrina A ; Coban, Zeynep ; Schumacher, Jill M ; Grompe, Markus ; Duncan, Andrew W ; Barton, Michelle Craig. / p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. In: Hepatology (Baltimore, Md.). 2013 ; Vol. 57, No. 5. pp. 2004-2013.

Bibtex

@article{a094dff2c84644e0b72ea97d463f8176,
title = "p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver",
abstract = " Functions of p53 during mitosis reportedly include prevention of polyploidy and transmission of aberrant chromosomes. However, whether p53 plays these roles during genomic surveillance in vivo and, if so, whether this is done via direct or indirect means remain unknown. The ability of normal, mature hepatocytes to respond to stimuli, reenter the cell cycle, and regenerate liver mass offers an ideal setting to assess mitosis in vivo. In quiescent liver, normally high ploidy levels in adult mice increased with loss of p53. Following partial hepatectomy, p53(-/-) hepatocytes exhibited early entry into the cell cycle and prolonged proliferation with an increased number of polyploid mitoses. Ploidy levels increased during regeneration of both wild-type (WT) and p53(-/-) hepatocytes, but only WT hepatocytes were able to dynamically resolve ploidy levels and return to normal by the end of regeneration. We identified multiple cell cycle and mitotic regulators, including Foxm1, Aurka, Lats2, Plk2, and Plk4, as directly regulated by chromatin interactions of p53 in vivo. Over a time course of regeneration, direct and indirect regulation of expression by p53 is mediated in a gene-specific manner.CONCLUSION: Our results show that p53 plays a role in mitotic fidelity and ploidy resolution in hepatocytes of normal and regenerative liver.",
keywords = "Animals, Cell Cycle/physiology, Cell Proliferation, Hepatectomy, Liver/pathology, Liver Regeneration/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitosis/physiology, Models, Animal, Ploidies, Transcription, Genetic/physiology, Tumor Suppressor Protein p53/deficiency",
author = "Svitlana Kurinna and Stratton, {Sabrina A} and Zeynep Coban and Schumacher, {Jill M} and Markus Grompe and Duncan, {Andrew W} and Barton, {Michelle Craig}",
note = "Copyright {\textcopyright} 2013 American Association for the Study of Liver Diseases.",
year = "2013",
month = may,
doi = "10.1002/hep.26233",
language = "English",
volume = "57",
pages = "2004--2013",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley & Sons Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver

AU - Kurinna, Svitlana

AU - Stratton, Sabrina A

AU - Coban, Zeynep

AU - Schumacher, Jill M

AU - Grompe, Markus

AU - Duncan, Andrew W

AU - Barton, Michelle Craig

N1 - Copyright © 2013 American Association for the Study of Liver Diseases.

PY - 2013/5

Y1 - 2013/5

N2 -  Functions of p53 during mitosis reportedly include prevention of polyploidy and transmission of aberrant chromosomes. However, whether p53 plays these roles during genomic surveillance in vivo and, if so, whether this is done via direct or indirect means remain unknown. The ability of normal, mature hepatocytes to respond to stimuli, reenter the cell cycle, and regenerate liver mass offers an ideal setting to assess mitosis in vivo. In quiescent liver, normally high ploidy levels in adult mice increased with loss of p53. Following partial hepatectomy, p53(-/-) hepatocytes exhibited early entry into the cell cycle and prolonged proliferation with an increased number of polyploid mitoses. Ploidy levels increased during regeneration of both wild-type (WT) and p53(-/-) hepatocytes, but only WT hepatocytes were able to dynamically resolve ploidy levels and return to normal by the end of regeneration. We identified multiple cell cycle and mitotic regulators, including Foxm1, Aurka, Lats2, Plk2, and Plk4, as directly regulated by chromatin interactions of p53 in vivo. Over a time course of regeneration, direct and indirect regulation of expression by p53 is mediated in a gene-specific manner.CONCLUSION: Our results show that p53 plays a role in mitotic fidelity and ploidy resolution in hepatocytes of normal and regenerative liver.

AB -  Functions of p53 during mitosis reportedly include prevention of polyploidy and transmission of aberrant chromosomes. However, whether p53 plays these roles during genomic surveillance in vivo and, if so, whether this is done via direct or indirect means remain unknown. The ability of normal, mature hepatocytes to respond to stimuli, reenter the cell cycle, and regenerate liver mass offers an ideal setting to assess mitosis in vivo. In quiescent liver, normally high ploidy levels in adult mice increased with loss of p53. Following partial hepatectomy, p53(-/-) hepatocytes exhibited early entry into the cell cycle and prolonged proliferation with an increased number of polyploid mitoses. Ploidy levels increased during regeneration of both wild-type (WT) and p53(-/-) hepatocytes, but only WT hepatocytes were able to dynamically resolve ploidy levels and return to normal by the end of regeneration. We identified multiple cell cycle and mitotic regulators, including Foxm1, Aurka, Lats2, Plk2, and Plk4, as directly regulated by chromatin interactions of p53 in vivo. Over a time course of regeneration, direct and indirect regulation of expression by p53 is mediated in a gene-specific manner.CONCLUSION: Our results show that p53 plays a role in mitotic fidelity and ploidy resolution in hepatocytes of normal and regenerative liver.

KW - Animals

KW - Cell Cycle/physiology

KW - Cell Proliferation

KW - Hepatectomy

KW - Liver/pathology

KW - Liver Regeneration/physiology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mitosis/physiology

KW - Models, Animal

KW - Ploidies

KW - Transcription, Genetic/physiology

KW - Tumor Suppressor Protein p53/deficiency

U2 - 10.1002/hep.26233

DO - 10.1002/hep.26233

M3 - Article

C2 - 23300120

VL - 57

SP - 2004

EP - 2013

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -