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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2

Xiaofeng Liu1, Yuqin Tan1, Chunfeng Zhang2

  • 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

EMBO Reports
|February 17, 2016
PubMed

Insights

The nucleolar protein NAT10 activates the tumor suppressor p53 by acetylating it and promoting Mdm2 degradation. This novel mechanism enhances genome stability and inhibits cancer cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The p53 protein is a critical tumor suppressor that maintains genome stability by initiating cell cycle arrest or apoptosis in response to cellular stress.
  • Nucleolar proteins are known to stabilize p53, but the precise mechanisms by which they activate p53 are not fully understood.
  • Understanding novel regulators of p53 activation is crucial for developing new cancer therapies.

Purpose of the Study:

  • To identify novel nucleolar proteins that regulate p53 activation.
  • To elucidate the molecular mechanisms by which NAT10 activates p53.
  • To investigate the role of NAT10 in cellular stress response and cancer.

Main Methods:

  • Western blotting to assess protein levels and modifications.
  • Immunoprecipitation to study protein interactions.
  • Cellular localization studies using immunofluorescence.
  • Cell proliferation assays.
  • Analysis of NAT10 expression in human colorectal cancer tissues.

Main Results:

  • NAT10 was identified as a novel regulator of p53 activation.
  • NAT10 acetylates p53 at lysine 120 (K120), stabilizing p53 by inhibiting Mdm2 binding.
  • NAT10 possesses E3 ligase activity that promotes Mdm2 degradation.
  • Following DNA damage, NAT10 translocates to the nucleoplasm, enhancing p53-mediated cell cycle control and apoptosis.
  • NAT10 expression is decreased in human colorectal carcinomas, correlating with inhibited cell proliferation.

Conclusions:

  • NAT10 plays a significant role in p53 activation through p53 acetylation and counteracting Mdm2.
  • NAT10 represents a novel pathway for nucleolar protein-mediated p53 activation as a cellular stress sensor.
  • NAT10's function in maintaining genome stability and inhibiting proliferation suggests its potential as a therapeutic target in cancer.
Keywords:
E3 ligaseMdm2NAT10acetylationp53

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