Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest
PDCD2 (programmed cell death domain 2) is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in...
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2014-08-01
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doaj-0d69793f6c9a4787926bc52e81e220ba2021-06-02T18:39:56ZengThe Company of BiologistsBiology Open2046-63902014-08-013982183110.1242/bio.2014832620148326Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrestCeline J. Granier0Wei Wang1Tiffany Tsang2Ruth Steward3Hatem E. Sabaawy4Mantu Bhaumik5Arnold B. Rabson6 Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA Sequencing and Microarray Core Facility, Lewis-Sigler Institute for Integrative Genetics, Princeton University, Princeton, NJ 08854, USA Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA Waksman Institute and Department of Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA PDCD2 (programmed cell death domain 2) is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs) and embryonic fibroblasts (MEFs). We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse.http://bio.biologists.org/content/3/9/821PDCD2Mouse embryoCell cycleProliferationESCsp53 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Celine J. Granier Wei Wang Tiffany Tsang Ruth Steward Hatem E. Sabaawy Mantu Bhaumik Arnold B. Rabson |
spellingShingle |
Celine J. Granier Wei Wang Tiffany Tsang Ruth Steward Hatem E. Sabaawy Mantu Bhaumik Arnold B. Rabson Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest Biology Open PDCD2 Mouse embryo Cell cycle Proliferation ESCs p53 |
author_facet |
Celine J. Granier Wei Wang Tiffany Tsang Ruth Steward Hatem E. Sabaawy Mantu Bhaumik Arnold B. Rabson |
author_sort |
Celine J. Granier |
title |
Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest |
title_short |
Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest |
title_full |
Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest |
title_fullStr |
Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest |
title_full_unstemmed |
Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest |
title_sort |
conditional inactivation of pdcd2 induces p53 activation and cell cycle arrest |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2014-08-01 |
description |
PDCD2 (programmed cell death domain 2) is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs) and embryonic fibroblasts (MEFs). We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse. |
topic |
PDCD2 Mouse embryo Cell cycle Proliferation ESCs p53 |
url |
http://bio.biologists.org/content/3/9/821 |
work_keys_str_mv |
AT celinejgranier conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT weiwang conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT tiffanytsang conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT ruthsteward conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT hatemesabaawy conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT mantubhaumik conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest AT arnoldbrabson conditionalinactivationofpdcd2inducesp53activationandcellcyclearrest |
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1721402134213165056 |