SUMOylation of mouse p53b by SUMO-1 promotes its pro-apoptotic function in ovarian granulosa cells

Xiao-Ming Liu1, Fei-Fei Yang, Yi-Feng Yuan

  • 1Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, People's Republic of China.

Plos One
|May 23, 2013
PubMed

Insights

SUMO-1 modification of p53b at lysine 375 is crucial for its stability and nuclear localization in mouse granulosa cells, thereby inducing apoptosis and potentially regulating follicular atresia.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cellular Apoptosis

Background:

  • Follicular atresia, the degradation of ovarian follicles, hinders mammalian ovary development.
  • Apoptosis of granulosa cells is a key mechanism in follicular atresia, with several related genes identified.
  • The specific roles of p53 and its post-translational modifications in mouse granulosa cell apoptosis remain largely unelucidated.

Purpose of the Study:

  • To investigate the function of p53 in mouse granulosa cells.
  • To explore the impact of SUMOylation on p53b stability, localization, and apoptotic activity.

Main Methods:

  • SUMOylation assays to determine p53b modification by SUMO-1 at lysine 375.
  • Immunofluorescence microscopy to assess the subcellular localization of wild-type and mutant p53b.
  • Gene expression analysis of apoptosis-related genes (e.g., Bax) and assessment of apoptosis levels following p53b overexpression.

Main Results:

  • Mouse p53b, not p53a, undergoes SUMOylation by SUMO-1 at lysine 375, enhancing its protein stability in a dose-dependent manner.
  • SUMOylation is essential for the nuclear localization of p53b in granulosa cells; the K375R mutant showed altered localization.
  • Overexpression of wild-type p53b, but not the SUMOylation-deficient mutant, significantly induced Bax expression and granulosa cell apoptosis.

Conclusions:

  • SUMO-1 modification of p53b at lysine 375 is critical for its apoptotic function in mouse granulosa cells.
  • This modification regulates p53b protein stability and nuclear import, suggesting a role in follicular atresia.
  • SUMO-1 conjugation of p53b may be a key regulatory mechanism controlling ovarian granulosa cell apoptosis and follicular development.

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