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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Bibliographic Details
Published in:Biology open 2014-09, Vol.3 (9), p.821-831
Main Authors: Granier, Celine J, Wang, Wei, Tsang, Tiffany, Steward, Ruth, Sabaawy, Hatem E, Bhaumik, Mantu, Rabson, Arnold B
Format: Article
Language:English
Subjects:
Apoptosis
Blastocysts
Cell activation
Cell cycle
Cell death
Danio rerio
Embryo cells
Embryo fibroblasts
Embryogenesis
Embryonic growth stage
ESCs
Fibroblasts
Gene deletion
Inactivation
Mouse embryo
p53
p53 Protein
PDCD2
Proliferation
Prolongation
Proteins
S phase
Splicing
Stem cell transplantation
Stem cells
Zebrafish
Zinc finger proteins
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Summary: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.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.20148326