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Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export

Yao Chen1, Hong Hai Li, Jing Fu

  • 1International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai 200438, China.

Cell Research
|November 28, 2007
PubMed

Insights

p28(GANK) oncoprotein inhibits nuclear factor-kappaB (NF-kappaB) signaling by binding to RelA and promoting its export from the nucleus. This mechanism suppresses NF-kappaB activity, suggesting a role in hepatocellular carcinoma progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • p28(GANK) (PSMD10) is an oncoprotein overexpressed in hepatocellular carcinoma, known to degrade p53 and Rb.
  • Nuclear factor-kappaB (NF-kappaB) activity is regulated by cytoplasmic sequestration, but other retention mechanisms are less understood.

Purpose of the Study:

  • To investigate the role of p28(GANK) in regulating NF-kappaB activity.
  • To elucidate the mechanism by which p28(GANK) affects NF-kappaB localization and function.

Main Methods:

  • Investigated the interaction between p28(GANK) and NF-kappaB/RelA.
  • Utilized a chromosomal region maintenance-1 (CRM-1) dependent pathway analysis.
  • Examined the role of ankyrin repeats and the N-terminal nuclear export sequence (NES) of p28(GANK).

Main Results:

  • p28(GANK) directly binds to NF-kappaB/RelA and mediates its export from the nucleus via a CRM-1 dependent pathway.
  • All ankyrin repeats of p28(GANK) are necessary for RelA interaction.
  • The N-terminal NES of p28(GANK) is crucial for inhibiting NF-kappaB/RelA nuclear translocation.

Conclusions:

  • p28(GANK) acts as a cytoplasmic retention factor for NF-kappaB/RelA.
  • Overexpression of p28(GANK) inhibits NF-kappaB/RelA nuclear localization and activity.
  • This mechanism highlights a novel pathway for NF-kappaB regulation by p28(GANK).

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