Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Celine J Granier1, Wei Wang2, Tiffany Tsang3

  • 1Child 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.

Biology Open
|August 24, 2014
PubMed

Insights

Programmed cell death domain 2 (PDCD2) regulates the cell cycle and p53 activation in early mouse development. Loss of PDCD2 causes G1 to S phase cell cycle arrest and increased p53 levels.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Programmed cell death domain 2 (PDCD2) is a conserved protein with unclear functions in mammalian development.
  • PDCD2 contains a zinc finger MYND domain, crucial for its activity.

Purpose of the Study:

  • To investigate the role of PDCD2 in mammalian early development.
  • To elucidate the molecular functions and cellular activities of PDCD2 in mouse embryonic stem cells (ESCs), embryonic fibroblasts (MEFs), and blastocysts.

Main Methods:

  • Generated mice with null or conditional knockout alleles for PDCD2.
  • Utilized tamoxifen-inducible knockout systems in MEFs and ESCs.
  • Analyzed cell cycle progression, p53 protein levels, and p53 target gene expression.

Main Results:

  • PDCD2 knockout in MEFs and ESCs caused G1 to S phase cell cycle progression defects.
  • Cell cycle arrest was associated with increased p53 protein and target gene levels.
  • PDCD2 deficiency in blastocysts also resulted in failure to enter S phase and elevated nuclear p53.

Conclusions:

  • PDCD2 plays a critical role in regulating cell cycle progression during early mouse embryonic development.
  • PDCD2 is involved in the control of p53 activation.
  • These findings highlight a unique function of PDCD2 in the interplay between cell cycle regulation and p53 signaling in early development.
Keywords:
Cell cycleESCsMouse embryoPDCD2Proliferationp53

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