title: Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest.
abstract: 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.
authors.affiliation: Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA rabsonab@rwjms.rutgers.edu graniecj@rwjms.rutgers.edu.
authors.forename: Celine J
authors.initials: CJ
authors.lastname: Granier
authors.affiliation: Sequencing and Microarray Core Facility, Lewis-Sigler Institute for Integrative Genetics, Princeton University, Princeton, NJ 08854, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tsang
authors.affiliation: Waksman Institute and Department of Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Steward
authors.affiliation: Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA.
authors.forename: Hatem E
authors.initials: HE
authors.lastname: Sabaawy
authors.affiliation: Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA.
authors.forename: Mantu
authors.initials: M
authors.lastname: Bhaumik
authors.affiliation: Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA rabsonab@rwjms.rutgers.edu graniecj@rwjms.rutgers.edu.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
keywords: Cell cycle; ESCs; Mouse embryo; PDCD2; Proliferation; p53